Nuclear size is sensitive to NTF2 protein levels in a manner dependent on Ran binding

Science.gov (United States)

Vuković, Lidija D.; Jevtić, Predrag; Zhang, Zhaojie; Stohr, Bradley A.; Levy, Daniel L.

2016-01-01

ABSTRACT Altered nuclear size is associated with many cancers, and determining whether cancer-associated changes in nuclear size contribute to carcinogenesis necessitates an understanding of mechanisms of nuclear size regulation. Although nuclear import rates generally positively correlate with nuclear size, NTF2 levels negatively affect nuclear size, despite the role of NTF2 (also known as NUTF2) in nuclear recycling of the import factor Ran. We show that binding of Ran to NTF2 is required for NTF2 to inhibit nuclear expansion and import of large cargo molecules in Xenopus laevis egg and embryo extracts, consistent with our observation that NTF2 reduces the diameter of the nuclear pore complex (NPC) in a Ran-binding-dependent manner. Furthermore, we demonstrate that ectopic NTF2 expression in Xenopus embryos and mammalian tissue culture cells alters nuclear size. Finally, we show that increases in nuclear size during melanoma progression correlate with reduced NTF2 expression, and increasing NTF2 levels in melanoma cells is sufficient to reduce nuclear size. These results show a conserved capacity for NTF2 to impact on nuclear size, and we propose that NTF2 might be a new cancer biomarker. PMID:26823604

SPRED: A machine learning approach for the identification of classical and non-classical secretory proteins in mammalian genomes

Energy Technology Data Exchange (ETDEWEB)

Kandaswamy, Krishna Kumar [Institute for Neuro- and Bioinformatics, University of Luebeck, 23538 Luebeck (Germany); Graduate School for Computing in Medicine and Life Sciences, University of Luebeck, 23538 Luebeck (Germany); Pugalenthi, Ganesan [School of Electrical and Electronic Engineering, Nanyang Technological University, Singapore 639798 (Singapore); Hartmann, Enno; Kalies, Kai-Uwe [Centre for Structural and Cell Biology in Medicine, Institute of Biology, University of Luebeck, 23538 Luebeck (Germany); Moeller, Steffen [Institute for Neuro- and Bioinformatics, University of Luebeck, 23538 Luebeck (Germany); Suganthan, P.N. [School of Electrical and Electronic Engineering, Nanyang Technological University, Singapore 639798 (Singapore); Martinetz, Thomas, E-mail: martinetz@inb.uni-luebeck.de [Institute for Neuro- and Bioinformatics, University of Luebeck, 23538 Luebeck (Germany)

2010-01-15

Eukaryotic protein secretion generally occurs via the classical secretory pathway that traverses the ER and Golgi apparatus. Secreted proteins usually contain a signal sequence with all the essential information required to target them for secretion. However, some proteins like fibroblast growth factors (FGF-1, FGF-2), interleukins (IL-1 alpha, IL-1 beta), galectins and thioredoxin are exported by an alternative pathway. This is known as leaderless or non-classical secretion and works without a signal sequence. Most computational methods for the identification of secretory proteins use the signal peptide as indicator and are therefore not able to identify substrates of non-classical secretion. In this work, we report a random forest method, SPRED, to identify secretory proteins from protein sequences irrespective of N-terminal signal peptides, thus allowing also correct classification of non-classical secretory proteins. Training was performed on a dataset containing 600 extracellular proteins and 600 cytoplasmic and/or nuclear proteins. The algorithm was tested on 180 extracellular proteins and 1380 cytoplasmic and/or nuclear proteins. We obtained 85.92% accuracy from training and 82.18% accuracy from testing. Since SPRED does not use N-terminal signals, it can detect non-classical secreted proteins by filtering those secreted proteins with an N-terminal signal by using SignalP. SPRED predicted 15 out of 19 experimentally verified non-classical secretory proteins. By scanning the entire human proteome we identified 566 protein sequences potentially undergoing non-classical secretion. The dataset and standalone version of the SPRED software is available at (http://www.inb.uni-luebeck.de/tools-demos/spred/spred).

SPRED: A machine learning approach for the identification of classical and non-classical secretory proteins in mammalian genomes

International Nuclear Information System (INIS)

Kandaswamy, Krishna Kumar; Pugalenthi, Ganesan; Hartmann, Enno; Kalies, Kai-Uwe; Moeller, Steffen; Suganthan, P.N.; Martinetz, Thomas

2010-01-01

Eukaryotic protein secretion generally occurs via the classical secretory pathway that traverses the ER and Golgi apparatus. Secreted proteins usually contain a signal sequence with all the essential information required to target them for secretion. However, some proteins like fibroblast growth factors (FGF-1, FGF-2), interleukins (IL-1 alpha, IL-1 beta), galectins and thioredoxin are exported by an alternative pathway. This is known as leaderless or non-classical secretion and works without a signal sequence. Most computational methods for the identification of secretory proteins use the signal peptide as indicator and are therefore not able to identify substrates of non-classical secretion. In this work, we report a random forest method, SPRED, to identify secretory proteins from protein sequences irrespective of N-terminal signal peptides, thus allowing also correct classification of non-classical secretory proteins. Training was performed on a dataset containing 600 extracellular proteins and 600 cytoplasmic and/or nuclear proteins. The algorithm was tested on 180 extracellular proteins and 1380 cytoplasmic and/or nuclear proteins. We obtained 85.92% accuracy from training and 82.18% accuracy from testing. Since SPRED does not use N-terminal signals, it can detect non-classical secreted proteins by filtering those secreted proteins with an N-terminal signal by using SignalP. SPRED predicted 15 out of 19 experimentally verified non-classical secretory proteins. By scanning the entire human proteome we identified 566 protein sequences potentially undergoing non-classical secretion. The dataset and standalone version of the SPRED software is available at (http://www.inb.uni-luebeck.de/tools-demos/spred/spred).

Unification of nonclassicality measures in interferometry

Science.gov (United States)

Yuan, Xiao; Zhou, Hongyi; Gu, Mile; Ma, Xiongfeng

2018-01-01

From an operational perspective, nonclassicality characterizes the exotic behavior in a physical process which cannot be explained with Newtonian physics. There are several widely used measures of nonclassicality, including coherence, discord, and entanglement, each proven to be essential resources in particular situations. There exists evidence of fundamental connections among the three measures. However, the sources of nonclassicality are still regarded differently and such connections are yet to be elucidated. Here, we introduce a general framework of defining a unified nonclassicality with an operational motivation founded on the capability of interferometry. Nonclassicality appears differently as coherence, discord, and entanglement in different scenarios with local measurement, weak basis-independent measurement, and strong basis-independent measurement, respectively. Our results elaborate how these three measures are related and how they can be transformed from each other. Experimental schemes are proposed to test the results.

Essential role of the small GTPase Ran in postnatal pancreatic islet development.

Directory of Open Access Journals (Sweden)

Fang Xia

Full Text Available The small GTPase Ran orchestrates pleiotropic cellular responses of nucleo-cytoplasmic shuttling, mitosis and subcellular trafficking, but whether deregulation of these pathways contributes to disease pathogenesis has remained elusive. Here, we generated transgenic mice expressing wild type (WT Ran, loss-of-function Ran T24N mutant or constitutively active Ran G19V mutant in pancreatic islet β cells under the control of the rat insulin promoter. Embryonic pancreas and islet development, including emergence of insulin(+ β cells, was indistinguishable in control or transgenic mice. However, by one month after birth, transgenic mice expressing any of the three Ran variants exhibited overt diabetes, with hyperglycemia, reduced insulin production, and nearly complete loss of islet number and islet mass, in vivo. Deregulated Ran signaling in transgenic mice, adenoviral over-expression of WT or mutant Ran in isolated islets, or short hairpin RNA (shRNA silencing of endogenous Ran in model insulinoma INS-1 cells, all resulted in decreased expression of the pancreatic and duodenal homeobox transcription factor, PDX-1, and reduced β cell proliferation, in vivo. These data demonstrate that a finely-tuned balance of Ran GTPase signaling is essential for postnatal pancreatic islet development and glucose homeostasis, in vivo.

Nonclassicality in phase-number uncertainty relations

International Nuclear Information System (INIS)

Matia-Hernando, Paloma; Luis, Alfredo

2011-01-01

We show that there are nonclassical states with lesser joint fluctuations of phase and number than any classical state. This is rather paradoxical since one would expect classical coherent states to be always of minimum uncertainty. The same result is obtained when we replace phase by a phase-dependent field quadrature. Number and phase uncertainties are assessed using variance and Holevo relation.

Nonclassicality in phase-number uncertainty relations

Energy Technology Data Exchange (ETDEWEB)

Matia-Hernando, Paloma; Luis, Alfredo [Departamento de Optica, Facultad de Ciencias Fisicas, Universidad Complutense, 28040 Madrid (Spain)

2011-12-15

We show that there are nonclassical states with lesser joint fluctuations of phase and number than any classical state. This is rather paradoxical since one would expect classical coherent states to be always of minimum uncertainty. The same result is obtained when we replace phase by a phase-dependent field quadrature. Number and phase uncertainties are assessed using variance and Holevo relation.

Nonclassical Problem for Ultraparabolic Equation in Abstract Spaces

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Gia Avalishvili

2016-01-01

Full Text Available Nonclassical problem for ultraparabolic equation with nonlocal initial condition with respect to one time variable is studied in abstract Hilbert spaces. We define the space of square integrable vector-functions with values in Hilbert spaces corresponding to the variational formulation of the nonlocal problem for ultraparabolic equation and prove trace theorem, which allows one to interpret initial conditions of the nonlocal problem. We obtain suitable a priori estimates and prove the existence and uniqueness of solution of the nonclassical problem and continuous dependence upon the data of the solution to the nonlocal problem. We consider an application of the obtained abstract results to nonlocal problem for ultraparabolic partial differential equation with second-order elliptic operator and obtain well-posedness result in Sobolev spaces.

Nonlinearity and nonclassicality in a nanomechanical resonator

Energy Technology Data Exchange (ETDEWEB)

Teklu, Berihu [Clermont Universite, Blaise Pascal University, CNRS, PHOTON-N2, Institut Pascal, Aubiere Cedex (France); Universita degli Studi di Milano, Dipartimento di Fisica, Milano (Italy); Ferraro, Alessandro; Paternostro, Mauro [Queen' s University, Centre for Theoretical Atomic, Molecular, and Optical Physics, School of Mathematics and Physics, Belfast (United Kingdom); Paris, Matteo G.A. [Universita degli Studi di Milano, Dipartimento di Fisica, Milano (Italy)

2015-12-15

We address quantitatively the relationship between the nonlinearity of a mechanical resonator and the nonclassicality of its ground state. In particular, we analyze the nonclassical properties of the nonlinear Duffing oscillator (being driven or not) as a paradigmatic example of a nonlinear nanomechanical resonator. We first discuss how to quantify the nonlinearity of this system and then show that the nonclassicality of the ground state, as measured by the volume occupied by the negative part of the Wigner function, monotonically increases with the nonlinearity in all the working regimes addressed in our study. Our results show quantitatively that nonlinearity is a resource to create nonclassical states in mechanical systems. (orig.)

RanBP3 influences interactions between CRM1 and its nuclear protein export substrates

OpenAIRE

Englmeier, Ludwig; Fornerod, Maarten; Bischoff, F. Ralf; Petosa, Carlo; Mattaj, Iain W.; Kutay, Ulrike

2001-01-01

We investigated the role of RanBP3, a nuclear member of the Ran-binding protein 1 family, in CRM1-mediated protein export in higher eukaryotes. RanBP3 interacts directly with CRM1 and also forms a trimeric complex with CRM1 and RanGTP. However, RanBP3 does not bind to CRM1 like an export substrate. Instead, it can stabilize CRM1–export substrate interaction. Nuclear RanBP3 stimulates CRM1-dependent protein export in permeabilized cells. These data indicate that RanBP3 functions by a novel mec...

Common Vocal Effects and Partial Glottal Vibration in Professional Nonclassical Singers.

Science.gov (United States)

Caffier, Philipp P; Ibrahim Nasr, Ahmed; Ropero Rendon, Maria Del Mar; Wienhausen, Sascha; Forbes, Eleanor; Seidner, Wolfram; Nawka, Tadeus

2018-05-01

To multidimensionally investigate common vocal effects in experienced professional nonclassical singers, to examine their mechanism of production and reproducibility, to demonstrate the existence of partial glottal vibration, and to assess the potential of damage to the voice from nonclassical singing. Individual cohort study. Ten male singers aged between 25 and 46 years (34 ± 7 years [mean ± SD]) with different stylistic backgrounds were recruited (five pop/rock/metal, five musical theater). Participants repeatedly presented the usual nonclassical vocal effects and techniques in their repertoire. All performances were documented and analyzed using established instruments (eg, auditory-perceptual assessment, videolaryngostroboscopy, electroglottography, voice function diagnostics). The vocal apparatus of all singers was healthy and capable of high performance. Typical nonclassical vocal effects were breathy voice, creaky voice, vocal fry, grunting, distortion, rattle, belt, and twang. All effects could be easily differentiated from each other. They were intraindividually consistently repeatable and also interindividually produced in a similar manner. A special feature in one singer was the first evidence of partial glottal vibration when belting in the high register. The unintended transition to this reduced voice quality was accompanied by physical fatigue and inflexible respiratory support. The long-lasting use of the investigated nonclassical vocal effects had no negative impact on trained singers. The possibility of long-term damage depends on the individual constitution, specific use, duration, and extent of the hyperfunction. The incidence of partial glottal vibration and its consequences require continuing research to learn more about efficient and healthy vocal function in nonclassical singing. Copyright © 2018 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

Higher-order nonclassical effects generated by multiple-photon annihilation-then-creation and creation-then-annihilation coherent states

International Nuclear Information System (INIS)

Yuan Hong-Chun; Xiao Jin; Xiong Chao; Zhu Xi-Fang; Xu Xue-Xiang

2016-01-01

We explore two observable nonclassical properties of quantum states generated by repeatedly operating annihilation-then-creation (AC) and creation-then-annihilation (CA) on the coherent state, respectively, such as higher-order sub-Poissonian statistics and higher-order squeezing-enhanced effect. The corresponding analytical expressions are derived in detail depending on m . By numerically comparing those quantum properties, it is found that these states above have very different nonclassical properties and nonclassicality is exhibited more strongly after AC operation than after CA operation. (paper)

Kinesin-1 and mitochondrial motility control by discrimination of structurally equivalent but distinct subdomains in Ran-GTP-binding domains of Ran-binding protein 2.

Science.gov (United States)

Patil, Hemangi; Cho, Kyoung-in; Lee, James; Yang, Yi; Orry, Andrew; Ferreira, Paulo A

2013-03-27

The pleckstrin homology (PH) domain is a versatile fold that mediates a variety of protein-protein and protein-phosphatidylinositol lipid interactions. The Ran-binding protein 2 (RanBP2) contains four interspersed Ran GTPase-binding domains (RBD(n = 1-4)) with close structural homology to the PH domain of Bruton's tyrosine kinase. The RBD2, kinesin-binding domain (KBD) and RBD3 comprise a tripartite domain (R2KR3) of RanBP2 that causes the unfolding, microtubule binding and biphasic activation of kinesin-1, a crucial anterograde motor of mitochondrial motility. However, the interplay between Ran GTPase and R2KR3 of RanBP2 in kinesin-1 activation and mitochondrial motility is elusive. We use structure-function, biochemical, kinetic and cell-based assays with time-lapse live-cell microscopy of over 260,000 mitochondrial-motility-related events to find mutually exclusive subdomains in RBD2 and RBD3 towards Ran GTPase binding, kinesin-1 activation and mitochondrial motility regulation. The RBD2 and RBD3 exhibit Ran-GTP-independent, subdomain and stereochemical-dependent discrimination on the biphasic kinetics of kinesin-1 activation or regulation of mitochondrial motility. Further, KBD alone and R2KR3 stimulate and suppress, respectively, multiple biophysical parameters of mitochondrial motility. The regulation of the bidirectional transport of mitochondria by either KBD or R2KR3 is highly coordinated, because their kinetic effects are accompanied always by changes in mitochondrial motile events of either transport polarity. These studies uncover novel roles in Ran GTPase-independent subdomains of RBD2 and RBD3, and KBD of RanBP2, that confer antagonizing and multi-modal mechanisms of kinesin-1 activation and regulation of mitochondrial motility. These findings open new venues towards the pharmacological harnessing of cooperative and competitive mechanisms regulating kinesins, RanBP2 or mitochondrial motility in disparate human disorders.

Identification of a novel NLS of herpes simplex virus type 1 (HSV-1) VP19C and its nuclear localization is required for efficient production of HSV-1.

Science.gov (United States)

Li, You; Zhao, Lei; Wang, Shuai; Xing, Junji; Zheng, Chunfu

2012-09-01

Herpes simplex virus type 1 (HSV-1) triplex is a complex of three protein subunits, consisting of two copies of VP23 and one copy of VP19C. Here, we identified a non-classical NLS of VP19C between aa 50 and 61, and the nuclear import of VP19C was mediated by RanGTP and importin β1-, but not importin α5-, dependent pathway. Additionally, recombinant virus harbouring this NLS mutation (NLSm) replicates less efficiently as wild-type. These data strongly suggested that the nuclear import of VP19C is required for efficient HSV-1 production.

Number-phase entropic squeezing and nonclassical properties of a three-level atom interacting with a two-mode field: intensity-dependent coupling, deformed Kerr medium, and detuning effects

Science.gov (United States)

Faghihi, Mohammad Javad; Tavassoly, Mohammad Kazem

2013-11-01

In this paper, we follow our presented model in J. Opt. Soc. Am. B {\\bf 30}, 1109--1117 (2013), in which the interaction between a $\\Lambda$-type three-level atom and a quantized two-mode radiation field in a cavity in the presence of nonlinearities is studied. After giving a brief review on the procedure of obtaining the state vector of the atom-field system, some further interesting and important physical features (which are of particular interest in the quantum optics field of research) of the whole system state, i.e., the number-phase entropic uncertainty relation (based on the two-mode Pegg-Barnett formalism) and some of the nonclassicality signs consist of sub-Poissonian statistics, Cauchy-Schwartz inequality and two kinds of squeezing phenomenon are investigated. During our presentation, the effects of intensity-dependent coupling, deformed Kerr medium and the detuning parameters on the depth and domain of each of the mentioned nonclassical criteria of the considered quantum system are studied, in detail. It is shown that each of the mentioned nonclassicality aspects can be obtained by appropriately choosing the related parameters.

The cyst nematode SPRYSEC protein RBP-1 elicits Gpa2- and RanGAP2-dependent plant cell death.

Directory of Open Access Journals (Sweden)

Melanie Ann Sacco

2009-08-01

Full Text Available Plant NB-LRR proteins confer robust protection against microbes and metazoan parasites by recognizing pathogen-derived avirulence (Avr proteins that are delivered to the host cytoplasm. Microbial Avr proteins usually function as virulence factors in compatible interactions; however, little is known about the types of metazoan proteins recognized by NB-LRR proteins and their relationship with virulence. In this report, we demonstrate that the secreted protein RBP-1 from the potato cyst nematode Globodera pallida elicits defense responses, including cell death typical of a hypersensitive response (HR, through the NB-LRR protein Gpa2. Gp-Rbp-1 variants from G. pallida populations both virulent and avirulent to Gpa2 demonstrated a high degree of polymorphism, with positive selection detected at numerous sites. All Gp-RBP-1 protein variants from an avirulent population were recognized by Gpa2, whereas virulent populations possessed Gp-RBP-1 protein variants both recognized and non-recognized by Gpa2. Recognition of Gp-RBP-1 by Gpa2 correlated to a single amino acid polymorphism at position 187 in the Gp-RBP-1 SPRY domain. Gp-RBP-1 expressed from Potato virus X elicited Gpa2-mediated defenses that required Ran GTPase-activating protein 2 (RanGAP2, a protein known to interact with the Gpa2 N terminus. Tethering RanGAP2 and Gp-RBP-1 variants via fusion proteins resulted in an enhancement of Gpa2-mediated responses. However, activation of Gpa2 was still dependent on the recognition specificity conferred by amino acid 187 and the Gpa2 LRR domain. These results suggest a two-tiered process wherein RanGAP2 mediates an initial interaction with pathogen-delivered Gp-RBP-1 proteins but where the Gpa2 LRR determines which of these interactions will be productive.

Aggresome formation is regulated by RanBPM through an interaction with HDAC6

Directory of Open Access Journals (Sweden)

Louisa M. Salemi

2014-05-01

Full Text Available In conditions of proteasomal impairment, the build-up of damaged or misfolded proteins activates a cellular response leading to the recruitment of damaged proteins into perinuclear aggregates called aggresomes. Aggresome formation involves the retrograde transport of cargo proteins along the microtubule network and is dependent on the histone deacetylase HDAC6. Here we show that ionizing radiation (IR promotes Ran-Binding Protein M (RanBPM relocalization into discrete perinuclear foci where it co-localizes with aggresome components ubiquitin, dynein and HDAC6, suggesting that the RanBPM perinuclear clusters correspond to aggresomes. RanBPM was also recruited to aggresomes following treatment with the proteasome inhibitor MG132 and the DNA-damaging agent etoposide. Strikingly, aggresome formation by HDAC6 was markedly impaired in RanBPM shRNA cells, but was restored by re-expression of RanBPM. RanBPM was found to interact with HDAC6 and to inhibit its deacetylase activity. This interaction was abrogated by a RanBPM deletion of its LisH/CTLH domain, which also prevented aggresome formation, suggesting that RanBPM promotes aggresome formation through an association with HDAC6. Our results suggest that RanBPM regulates HDAC6 activity and is a central regulator of aggresome formation.

Incomplete Detection of Nonclassical Phase-Space Distributions

Science.gov (United States)

Bohmann, M.; Tiedau, J.; Bartley, T.; Sperling, J.; Silberhorn, C.; Vogel, W.

2018-02-01

We implement the direct sampling of negative phase-space functions via unbalanced homodyne measurement using click-counting detectors. The negativities significantly certify nonclassical light in the high-loss regime using a small number of detectors which cannot resolve individual photons. We apply our method to heralded single-photon states and experimentally demonstrate the most significant certification of nonclassicality for only two detection bins. By contrast, the frequently applied Wigner function fails to directly indicate such quantum characteristics for the quantum efficiencies present in our setup without applying additional reconstruction algorithms. Therefore, we realize a robust and reliable approach to characterize nonclassical light in phase space under realistic conditions.

Nonclassical correlations in superconducting circuits

Energy Technology Data Exchange (ETDEWEB)

Migliore, Rosanna [Dipartimento di Scienze Fisiche ed Astronomiche, Universita di Palermo (Italy); CNR-INFM, UdR CNISM di Palermo, Palermo (Italy); Scala, Matteo [Dipartimento di Scienze Fisiche ed Astronomiche, Universita di Palermo (Italy); Departamento de Optica, Facultad de Fisica, Universidad Complutense, Madrid (Spain); Guccione, Marina; Sanchez-Soto, Luis L. [Dipartimento di Scienze Fisiche ed Astronomiche, Universita di Palermo (Italy); Messina, Antonino [Departamento de Optica, Facultad de Fisica, Universidad Complutense, Madrid (Spain)

2009-05-15

A key step on the road map to solid-state quantum information processing (and to a deeper understanding of many counterintuitive aspects of quantum mechanics) is the generation and manipulation of nonclassical correlations between different quantum systems. Within this framework, we analyze the possibility of generating maximally entangled states in a system of two superconducting flux qubits, as well as the effectof their own environments on the entanglement dynamics. The analysis reported here confirms that the phenomena of sudden birth and sudden death of the entanglement do not depend on the particular measure of the entanglement adopted (copyright 2009 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim) (orig.)

Treatment of Nonclassic 11-Hydroxylase Deficiency with Ashwagandha Root

Directory of Open Access Journals (Sweden)

Daniel Powell

2017-01-01

Full Text Available An elderly woman presented with acne and male pattern alopecia, which upon diagnostic evaluation was found to be due to nonclassic 11-hydroxylase deficiency. We previously reported that Ashwagandha root ameliorates nonclassic 3-β-ol dehydrogenase and aldosterone synthase deficiencies. This is the first report of its use being associated with amelioration of nonclassic 11-hydroxylase deficiency, where its apparent effects appear to be dose-related.

Concrete damage diagnosed using the non-classical nonlinear acoustic method

International Nuclear Information System (INIS)

Dao, Zhou; Xiao-Zhou, Liu; Xiu-Fen, Gong; E, Nazarov V; Li, Ma

2009-01-01

It is known that the strength of concrete is seriously affected by damage and cracking. In this paper, six concrete samples under different damage levels are studied. The experimental results show a linear dependence of the resonance frequency shift on strain amplitude at the fundamental frequency, and approximate quadratic dependence of the amplitudes of the second and third harmonics on strain amplitude at the fundamental frequency as well. In addition, the amplitude of the third harmonics is shown to increase with the increase of damage level, which is even higher than that of the second harmonics in samples with higher damage levels. These are three properties of non-classical nonlinear acoustics. The nonlinear parameters increase from 10 6 to 10 8 with damage level, and are more sensitive to the damage level of the concrete than the linear parameters obtained by using traditional acoustics methods. So, this method based on non-classical nonlinear acoustics may provide a better means of non-destructive testing (NDT) of concrete and other porous materials

Nonclassical properties of a contradirectional nonlinear optical coupler

Energy Technology Data Exchange (ETDEWEB)

Thapliyal, Kishore [Jaypee Institute of Information Technology, A-10, Sector-62, Noida, UP-201307 (India); Pathak, Anirban, E-mail: anirban.pathak@gmail.com [Jaypee Institute of Information Technology, A-10, Sector-62, Noida, UP-201307 (India); RCPTM, Joint Laboratory of Optics of Palacky University and Institute of Physics of Academy of Science of the Czech Republic, Faculty of Science, Palacky University, 17. listopadu 12, 771 46 Olomouc (Czech Republic); Sen, Biswajit [Department of Physics, Vidyasagar Teachers' Training College, Midnapore 721101 (India); Perřina, Jan [RCPTM, Joint Laboratory of Optics of Palacky University and Institute of Physics of Academy of Science of the Czech Republic, Faculty of Science, Palacky University, 17. listopadu 12, 771 46 Olomouc (Czech Republic); Department of Optics, Palacky University, 17. listopadu 12, 771 46 Olomouc (Czech Republic)

2014-10-24

We investigate the nonclassical properties of output fields propagated through a contradirectional asymmetric nonlinear optical coupler consisting of a linear waveguide and a nonlinear (quadratic) waveguide operated by second harmonic generation. In contrast to the earlier results, all the initial fields are considered weak and a completely quantum-mechanical model is used here to describe the system. Perturbative solutions of Heisenberg's equations of motion for various field modes are obtained using Sen–Mandal technique. Obtained solutions are subsequently used to show the existence of single-mode and intermodal squeezing, single-mode and intermodal antibunching, two-mode and multi-mode entanglement in the output of contradirectional asymmetric nonlinear optical coupler. Further, existence of higher order nonclassicality is also established by showing the existence of higher order antibunching, higher order squeezing and higher order entanglement. Variation of observed nonclassical characters with different coupling constants and phase mismatch is discussed. - Highlights: • Nonclassicalities in fields propagating through a directional coupler is studied. • Completely quantum-mechanical description of the coupler is provided. • Analytic solutions of Heisenberg equations of motion for various modes are obtained. • Existence of lower order and higher order entanglement is shown. • Variation of nonclassicalities with phase-mismatch and coupling constants is studied.

Angular-momentum nonclassicality by breaking classical bounds on statistics

Energy Technology Data Exchange (ETDEWEB)

Luis, Alfredo [Departamento de Optica, Facultad de Ciencias Fisicas, Universidad Complutense, E-28040 Madrid (Spain); Rivas, Angel [Departamento de Fisica Teorica I, Facultad de Ciencias Fisicas, Universidad Complutense, E-28040 Madrid (Spain)

2011-10-15

We derive simple practical procedures revealing the quantum behavior of angular momentum variables by the violation of classical upper bounds on the statistics. Data analysis is minimum and definite conclusions are obtained without evaluation of moments, or any other more sophisticated procedures. These nonclassical tests are very general and independent of other typical quantum signatures of nonclassical behavior such as sub-Poissonian statistics, squeezing, or oscillatory statistics, being insensitive to the nonclassical behavior displayed by other variables.

Nonclassical effects in plasmonics: an energy perspective to quantify nonclassical effects

DEFF Research Database (Denmark)

Yan, Wei; Mortensen, N. Asger

2016-01-01

of the nonclassical effects at different microscopic levels by contrasting the numerical results from the semiclassical hydrodynamic Drude model (HDM) and the microscopic random-phase approximation (RPA). The formal relation between the HDM and the RPA is also established for metals by exploring the limit...

Fisher information, nonclassicality and quantum revivals

Energy Technology Data Exchange (ETDEWEB)

Romera, Elvira [Instituto Carlos I de Física Teórica y Computacional, Universidad de Granada, Fuentenueva s/n, 18071 Granada (Spain); Departamento de Física Atómica, Molecular y Nuclear, Universidad de Granada, Fuentenueva s/n, 18071 Granada (Spain); Santos, Francisco de los, E-mail: dlsantos@onsager.ugr.es [Instituto Carlos I de Física Teórica y Computacional, Universidad de Granada, Fuentenueva s/n, 18071 Granada (Spain); Departamento de Electromagnetismo y Física de la Materia, Universidad de Granada, Fuentenueva s/n, 18071 Granada (Spain)

2013-11-08

Wave packet revivals and fractional revivals are studied by means of a measure of nonclassicality based on the Fisher information. In particular, we show that the spreading and the regeneration of initially Gaussian wave packets in a quantum bouncer and in the infinite square-well correspond, respectively, to high and low nonclassicality values. This result is in accordance with the physical expectations that at a quantum revival wave packets almost recover their initial shape and the classical motion revives temporarily afterward.

Fisher information, nonclassicality and quantum revivals

International Nuclear Information System (INIS)

Romera, Elvira; Santos, Francisco de los

2013-01-01

Wave packet revivals and fractional revivals are studied by means of a measure of nonclassicality based on the Fisher information. In particular, we show that the spreading and the regeneration of initially Gaussian wave packets in a quantum bouncer and in the infinite square-well correspond, respectively, to high and low nonclassicality values. This result is in accordance with the physical expectations that at a quantum revival wave packets almost recover their initial shape and the classical motion revives temporarily afterward.

RanBP2 modulates Cox11 and hexokinase I activities and haploinsufficiency of RanBP2 causes deficits in glucose metabolism.

Directory of Open Access Journals (Sweden)

Azamat Aslanukov

2006-10-01

Full Text Available The Ran-binding protein 2 (RanBP2 is a large multimodular and pleiotropic protein. Several molecular partners with distinct functions interacting specifically with selective modules of RanBP2 have been identified. Yet, the significance of these interactions with RanBP2 and the genetic and physiological role(s of RanBP2 in a whole-animal model remain elusive. Here, we report the identification of two novel partners of RanBP2 and a novel physiological role of RanBP2 in a mouse model. RanBP2 associates in vitro and in vivo and colocalizes with the mitochondrial metallochaperone, Cox11, and the pacemaker of glycolysis, hexokinase type I (HKI via its leucine-rich domain. The leucine-rich domain of RanBP2 also exhibits strong chaperone activity toward intermediate and mature folding species of Cox11 supporting a chaperone role of RanBP2 in the cytosol during Cox11 biogenesis. Cox11 partially colocalizes with HKI, thus supporting additional and distinct roles in cell function. Cox11 is a strong inhibitor of HKI, and RanBP2 suppresses the inhibitory activity of Cox11 over HKI. To probe the physiological role of RanBP2 and its role in HKI function, a mouse model harboring a genetically disrupted RanBP2 locus was generated. RanBP2(-/- are embryonically lethal, and haploinsufficiency of RanBP2 in an inbred strain causes a pronounced decrease of HKI and ATP levels selectively in the central nervous system. Inbred RanBP2(+/- mice also exhibit deficits in growth rates and glucose catabolism without impairment of glucose uptake and gluconeogenesis. These phenotypes are accompanied by a decrease in the electrophysiological responses of photosensory and postreceptoral neurons. Hence, RanBP2 and its partners emerge as critical modulators of neuronal HKI, glucose catabolism, energy homeostasis, and targets for metabolic, aging disorders and allied neuropathies.

RanBP2 modulates Cox11 and hexokinase I activities and haploinsufficiency of RanBP2 causes deficits in glucose metabolism.

Science.gov (United States)

Aslanukov, Azamat; Bhowmick, Reshma; Guruju, Mallikarjuna; Oswald, John; Raz, Dorit; Bush, Ronald A; Sieving, Paul A; Lu, Xinrong; Bock, Cheryl B; Ferreira, Paulo A

2006-10-01

The Ran-binding protein 2 (RanBP2) is a large multimodular and pleiotropic protein. Several molecular partners with distinct functions interacting specifically with selective modules of RanBP2 have been identified. Yet, the significance of these interactions with RanBP2 and the genetic and physiological role(s) of RanBP2 in a whole-animal model remain elusive. Here, we report the identification of two novel partners of RanBP2 and a novel physiological role of RanBP2 in a mouse model. RanBP2 associates in vitro and in vivo and colocalizes with the mitochondrial metallochaperone, Cox11, and the pacemaker of glycolysis, hexokinase type I (HKI) via its leucine-rich domain. The leucine-rich domain of RanBP2 also exhibits strong chaperone activity toward intermediate and mature folding species of Cox11 supporting a chaperone role of RanBP2 in the cytosol during Cox11 biogenesis. Cox11 partially colocalizes with HKI, thus supporting additional and distinct roles in cell function. Cox11 is a strong inhibitor of HKI, and RanBP2 suppresses the inhibitory activity of Cox11 over HKI. To probe the physiological role of RanBP2 and its role in HKI function, a mouse model harboring a genetically disrupted RanBP2 locus was generated. RanBP2(-/-) are embryonically lethal, and haploinsufficiency of RanBP2 in an inbred strain causes a pronounced decrease of HKI and ATP levels selectively in the central nervous system. Inbred RanBP2(+/-) mice also exhibit deficits in growth rates and glucose catabolism without impairment of glucose uptake and gluconeogenesis. These phenotypes are accompanied by a decrease in the electrophysiological responses of photosensory and postreceptoral neurons. Hence, RanBP2 and its partners emerge as critical modulators of neuronal HKI, glucose catabolism, energy homeostasis, and targets for metabolic, aging disorders and allied neuropathies.

Converting multilevel nonclassicality into genuine multipartite entanglement

Science.gov (United States)

Regula, Bartosz; Piani, Marco; Cianciaruso, Marco; Bromley, Thomas R.; Streltsov, Alexander; Adesso, Gerardo

2018-03-01

Characterizing genuine quantum resources and determining operational rules for their manipulation are crucial steps to appraise possibilities and limitations of quantum technologies. Two such key resources are nonclassicality, manifested as quantum superposition between reference states of a single system, and entanglement, capturing quantum correlations among two or more subsystems. Here we present a general formalism for the conversion of nonclassicality into multipartite entanglement, showing that a faithful reversible transformation between the two resources is always possible within a precise resource-theoretic framework. Specializing to quantum coherence between the levels of a quantum system as an instance of nonclassicality, we introduce explicit protocols for such a mapping. We further show that the conversion relates multilevel coherence and multipartite entanglement not only qualitatively, but also quantitatively, restricting the amount of entanglement achievable in the process and in particular yielding an equality between the two resources when quantified by fidelity-based geometric measures.

Tomography of nonclassical states

NARCIS (Netherlands)

Bazrafkan, MR; Man'ko, [No Value

2003-01-01

A review of the symplectic tomography method is presented. Superpositions of different types of photon states are considered within the framework of the tomography approach. Such nonclassical photon states as even and odd coherent states, crystallized Schrodinger cat states, and other superposition

Testing nonclassicality in multimode fields: A unified derivation of classical inequalities

International Nuclear Information System (INIS)

Miranowicz, Adam; Bartkowiak, Monika; Wang Xiaoguang; Liu Yuxi; Nori, Franco

2010-01-01

We consider a way to generate operational inequalities to test nonclassicality (or quantumness) of multimode bosonic fields (or multiparty bosonic systems) that unifies the derivation of many known inequalities and allows to propose new ones. The nonclassicality criteria are based on Vogel's criterion corresponding to analyzing the positivity of multimode P functions or, equivalently, the positivity of matrices of expectation values of, e.g., creation and annihilation operators. We analyze not only monomials but also polynomial functions of such moments, which can sometimes enable simpler derivations of physically relevant inequalities. As an example, we derive various classical inequalities which can be violated only by nonclassical fields. In particular, we show how the criteria introduced here easily reduce to the well-known inequalities describing (a) multimode quadrature squeezing and its generalizations, including sum, difference, and principal squeezing; (b) two-mode one-time photon-number correlations, including sub-Poisson photon-number correlations and effects corresponding to violations of the Cauchy-Schwarz and Muirhead inequalities; (c) two-time single-mode photon-number correlations, including photon antibunching and hyperbunching; and (d) two- and three-mode quantum entanglement. Other simple inequalities for testing nonclassicality are also proposed. We have found some general relations between the nonclassicality and entanglement criteria, in particular those resulting from the Cauchy-Schwarz inequality. It is shown that some known entanglement inequalities can be derived as nonclassicality inequalities within our formalism, while some other known entanglement inequalities can be seen as sums of more than one inequality derived from the nonclassicality criterion. This approach enables a deeper analysis of the entanglement for a given nonclassicality.

Dynamics of entropy and nonclassical properties of the state of a Λ-type three-level atom interacting with a single-mode cavity field with intensity-dependent coupling in a Kerr medium

International Nuclear Information System (INIS)

Faghihi, M J; Tavassoly, M K

2012-01-01

In this paper, we study the interaction between a three-level atom and a quantized single-mode field with ‘intensity-dependent coupling’ in a ‘Kerr medium’. The three-level atom is considered to be in a Λ-type configuration. Under particular initial conditions, which may be prepared for the atom and the field, the dynamical state vector of the entire system will be explicitly obtained, for the arbitrary nonlinearity function f(n) associated with any physical system. Then, after evaluating the variation of the field entropy against time, we will investigate the quantum statistics as well as some of the nonclassical properties of the introduced state. During our calculations we investigate the effects of intensity-dependent coupling, Kerr medium and detuning parameters on the depth and domain of the nonclassicality features of the atom–field state vector. Finally, we compare our obtained results with those of V-type three-level atoms. (paper)

Dynamics of entropy and nonclassical properties of the state of a Λ-type three-level atom interacting with a single-mode cavity field with intensity-dependent coupling in a Kerr medium

Science.gov (United States)

Faghihi, M. J.; Tavassoly, M. K.

2012-02-01

In this paper, we study the interaction between a three-level atom and a quantized single-mode field with ‘intensity-dependent coupling’ in a ‘Kerr medium’. The three-level atom is considered to be in a Λ-type configuration. Under particular initial conditions, which may be prepared for the atom and the field, the dynamical state vector of the entire system will be explicitly obtained, for the arbitrary nonlinearity function f(n) associated with any physical system. Then, after evaluating the variation of the field entropy against time, we will investigate the quantum statistics as well as some of the nonclassical properties of the introduced state. During our calculations we investigate the effects of intensity-dependent coupling, Kerr medium and detuning parameters on the depth and domain of the nonclassicality features of the atom-field state vector. Finally, we compare our obtained results with those of V-type three-level atoms.

Non-classical structures of organic compounds: unusual stereochemistry and hypercoordination

International Nuclear Information System (INIS)

Minkin, Vladimir I; Minyaev, Ruslan M; Hoffmann, Roald

2002-01-01

Non-classical structures of organic compounds are defined as molecules containing non-tetrahedral tetracoordinate and/or hypercoordinate carbon atoms. The evolution of the views on this subject is considered and the accumulated theoretical and experimental data on the structures and dynamic transformations of non-classical organic compounds are systematised. It is shown that computational analysis using the methods and the software potential of modern quantum chemistry has now acquired high predictive capacity and is the most important source of data on the structures of non-classical compounds. The bibliography includes 227 references.

Skeletal muscle wasting: new role of nonclassical renin-angiotensin system.

Science.gov (United States)

Cabello-Verrugio, Claudio; Rivera, Juan C; Garcia, Dominga

2017-05-01

Skeletal muscle can be affected by many physiological and pathological conditions that contribute to the development of muscle weakness, including skeletal muscle loss, inflammatory processes, or fibrosis. Therefore, research into therapeutic treatment alternatives or alleviation of these effects on skeletal muscle is of great importance. Recent studies have shown that angiotensin (1-7) [Ang-(1-7)] - a vasoactive peptide of the nonclassical axis in the renin-angiotensin system (RAS) - and its Mas receptor are expressed in skeletal muscle. Ang-(1-7), through its Mas receptor, prevents or diminishes deleterious effects induced by skeletal muscle disease or injury. Specifically, the Ang-(1-7)-Mas receptor axis modulates molecular mechanisms involved in muscle mass regulation, such as the ubiquitin proteasome pathway, the insulin-like growth factor type 1/Akt (protein kinase B) pathway, or myonuclear apoptosis, and also inflammation and fibrosis pathways. Although further research into this topic and the possible side effects of Ang-(1-7) is necessary, these findings are promising, and suggest that the Ang-(1-7)-Mas axis can be considered a possible therapeutic target for treating patients with muscular disorders.

On the origin of nonclassicality in single systems

International Nuclear Information System (INIS)

Aravinda, S; Srikanth, R; Pathak, Anirban

2017-01-01

In the framework of certain general probability theories of single systems, we identify various nonclassical features such as incompatibility, multiple pure-state decomposability, measurement disturbance, no-cloning and the impossibility of certain universal operations, with the non-simpliciality of the state space. This is shown to naturally suggest an underlying simplex as an ontological model. Contextuality turns out to be an independent nonclassical feature, arising from the intransitivity of compatibility. (paper)

Cauchy–Schwarz inequality-based criteria for the non-classicality of sub-Poisson and antibunched light

Energy Technology Data Exchange (ETDEWEB)

Volovich, Igor V., E-mail: volovich@mi.ras.ru

2016-01-08

We discuss non-classicality of photon antibunching and sub-Poisson photon statistics. The difference K between the variance and the mean of the particle number operator as a measure of non-classicality of a state is discussed. The non-classicality of quantum states, discussed here, is different from another non-classicality, related with Bell's inequalities and entanglement though both can be traced to the violation of an inequality implied by an assumption of classicality that utilized the Cauchy–Schwarz inequality in the derivation. - Highlights: • Non-classicality of photon antibunching and sub-Poisson statistics are discussed. • The Cauchy–Schwarz inequality provides criteria for the non-classicality. • The vacuum contribution makes the superposition of quantum states more classical. • Experiments to generate non-classical superpositions of the Fock states are suggested.

Ran Involved in the Development and Reproduction Is a Potential Target for RNA-Interference-Based Pest Management in Nilaparvata lugens.

Directory of Open Access Journals (Sweden)

Kai-Long Li

Full Text Available Ran (RanGTPase in insects participates in the 20-hydroxyecdysone signal transduction pathway in which downstream genes, FTZ-F1, Krüppel-homolog 1 (Kr-h1 and vitellogenin, are involved. A putative Ran gene (NlRan was cloned from Nilaparvata lugens, a destructive phloem-feeding pest of rice. NlRan has the typical Ran primary structure features that are conserved in insects. NlRan showed higher mRNA abundance immediately after molting and peaked in newly emerged female adults. Among the examined tissues ovary had the highest transcript level, followed by fat body, midgut and integument, and legs. Three days after dsNlRan injection the NlRan mRNA abundance in the third-, fourth-, and fifth-instar nymphs was decreased by 94.3%, 98.4% and 97.0%, respectively. NlFTZ-F1 expression levels in treated third- and fourth-instar nymphs were reduced by 89.3% and 23.8%, respectively. In contrast, NlKr-h1 mRNA levels were up-regulated by 67.5 and 1.5 folds, respectively. NlRan knockdown significantly decreased the body weights, delayed development, and killed >85% of the nymphs at day seven. Two apparent phenotypic defects were observed: (1 Extended body form, and failed to molt; (2 The cuticle at the notum was split open but cannot completely shed off. The newly emerged female adults from dsNlRan injected fifth-instar nymphs showed lower levels of NlRan and vitellogenin, lower weight gain and honeydew excretion comparing with the blank control, and no offspring. Those results suggest that NlRan encodes a functional protein that was involved in development and reproduction. The study established proof of concept that NlRan could serve as a target for dsRNA-based pesticides for N. lugens control.

Entanglement and Other Nonclassical Properties of Two Two-Level Atoms Interacting with a Two-Mode Binomial Field: Constant and Intensity-Dependent Coupling Regimes

International Nuclear Information System (INIS)

Tavassoly, M.K.; Hekmatara, H.

2015-01-01

In this paper, we consider the interaction between two two-level atoms and a two-mode binomial field with a general intensity-dependent coupling regime. The outlined dynamical problem has explicit analytical solution, by which we can evaluate a few of its physical features of interest. To achieve the purpose of the paper, after choosing a particular nonlinearity function, we investigate the quantum statistics, atomic population inversion and at last the linear entropy of the atom-field system which is a good measure for the degree of entanglement. In detail, the effects of binomial field parameters, in addition to different initial atomic states on the temporal behavior of the mentioned quantities have been analyzed. The results show that, the values of binomial field parameters and the initial state of the two atoms influence on the nonclassical effects in the obtained states through which one can tune the nonclassicality criteria appropriately. Setting intensity-dependent coupling function equal to 1 reduces the results to the constant coupling case. By comparing the latter case with the nonlinear regime, we will observe that the nonlinearity disappears the pattern of collapse-revival phenomenon in the evolution of Mandel parameter and population inversion (which can be seen in the linear case with constant coupling), however, more typical collapse-revivals will be appeared for the cross-correlation function in the nonlinear case. Finally, in both linear and nonlinear regime, the entropy remains less than (but close to) 0.5. In other words the particular chosen nonlinearity does not critically affect on the entropy of the system. (paper)

RCC1 regulates inner centromeric composition in a Ran-independent fashion.

Science.gov (United States)

Zhang, Michael Shaofei; Furuta, Maiko; Arnaoutov, Alexei; Dasso, Mary

2018-01-01

RCC1 associates to chromatin dynamically within mitosis and catalyzes Ran-GTP production. Exogenous RCC1 disrupts kinetochore structure in Xenopus egg extracts (XEEs), but the molecular basis of this disruption remains unknown. We have investigated this question, utilizing replicated chromosomes that possess paired sister kinetochores. We find that exogenous RCC1 evicts a specific subset of inner KT proteins including Shugoshin-1 (Sgo1) and the chromosome passenger complex (CPC). We generated RCC1 mutants that separate its enzymatic activity and chromatin binding. Strikingly, Sgo1 and CPC eviction depended only on RCC1's chromatin affinity but not its capacity to produce Ran-GTP. RCC1 similarly released Sgo1 and CPC from synthetic kinetochores assembled on CENP-A nucleosome arrays. Together, our findings indicate RCC1 regulates kinetochores at the metaphase-anaphase transition through Ran-GTP-independent displacement of Sgo1 and CPC.

Classical and nonclassical symmetries analysis for initial value problems

International Nuclear Information System (INIS)

Zhang Zhiyong; Chen Yufu

2010-01-01

Classical and nonclassical symmetries are considered to reduce evolution equations with initial conditions in two independent variables. First of all, we rearrange the classical infinitesimal operators such that they leave the initial value problems invariant. Secondly, we give a sufficient condition for the nonclassical symmetry reductions of initial value problems. The generalized Kuramoto-Sivashinsky equation with dispersive effects is considered to examine the algorithms.

Nonclassical pseudospectral method for the solution of brachistochrone problem

International Nuclear Information System (INIS)

Alipanah, A.; Razzaghi, M.; Dehghan, M.

2007-01-01

In this paper, nonclassical pseudospectral method is proposed for solving the classic brachistochrone problem. The brachistochrone problem is first formulated as a nonlinear optimal control problem. Properties of nonclassical pseudospectral method are presented, these properties are then utilized to reduce the computation of brachistochrone problem to the solution of algebraic equations. Using this method, the solution to the brachistochrone problem is compared with those in the literature

About the nonclassicality of states defined by nonpositivity of the P-quasiprobability

International Nuclear Information System (INIS)

Wuensche, Alfred

2004-01-01

The definition of nonclassical states in quantum optics by the nonpositivity of their Glauber-Sudarshan quasiprobability P(α,α * )-P(q,p) is investigated and it is shown that it hides some serious problems. It leads to a subdivision of squeezed thermal states into classical and nonclassical states which is difficult to interpret physically by some qualitatively different behaviour of the states. Nonclassical states are found in arbitrarily small neighbourhoods of every classical state that is illustrated by a very artificial modified thermal state. The observability of the criterion in comparison to that for nonclassicality of states determined by the nearest Hilbert-Schmidt distance to a class of reference states is discussed. The behaviour of the nonclassicality of states in models of phase-insensitive processes of damping and amplification is investigated and it is found that every nonclassical state eventually makes a transition to a classical state. However, this is not specific for the negativities or singularities of the Glauber-Sudarshan quasiprobability and is found in similar form for other quasiprobabilities, for example, for the Wigner quasiprobability. We discuss in quite general form some defects of the Glauber-Sudarshan quasiprobability if compared with classical distribution functions over the phase space, in particular the failure of an earlier advertised superposition formula

Nonclassical states of light with a smooth P function

Science.gov (United States)

Damanet, François; Kübler, Jonas; Martin, John; Braun, Daniel

2018-02-01

There is a common understanding in quantum optics that nonclassical states of light are states that do not have a positive semidefinite and sufficiently regular Glauber-Sudarshan P function. Almost all known nonclassical states have P functions that are highly irregular, which makes working with them difficult and direct experimental reconstruction impossible. Here we introduce classes of nonclassical states with regular, non-positive-definite P functions. They are constructed by "puncturing" regular smooth positive P functions with negative Dirac-δ peaks or other sufficiently narrow smooth negative functions. We determine the parameter ranges for which such punctures are possible without losing the positivity of the state, the regimes yielding antibunching of light, and the expressions of the Wigner functions for all investigated punctured states. Finally, we propose some possible experimental realizations of such states.

Nonclassicality indicator for the real phase-space distribution functions

International Nuclear Information System (INIS)

Sadeghi, Parvin; Khademi, Siamak; Nasiri, Sadollah

2010-01-01

Benedict et al. and Kenfack et al. advocated nonclassicality indicators based on the measurement of negativity of the Wigner distribution functions. These indicators have some applications in quantum mechanics and quantum optics. In this paper we define a nonclassicality indicator in terms of the interference in phase space, which is applicable to some real distribution functions including those of Wigner. As a special case one may reproduce the previous results using our indicator for the Wigner distribution functions. This indicator is examined for cases of the Schroedinger cat state and the thermal states and the results are compared with those obtained by previous methods. It seems that the physical behavior of nonclassicality indicators originates in the uncertainty principle. This is shown by an onto correspondence between these indicators and the uncertainty principle.

Nonclassical Symmetries for Nonlinear Partial Differential Equations via Compatibility

International Nuclear Information System (INIS)

El-Sabbagh, Mostafa F.; Ahmad, Ali T.

2011-01-01

The determining equations for the nonclassical symmetry reductions of nonlinear partial differential equations with arbitrary order can be obtained by requiring the compatibility between the original equations and the invariant surface conditions. The (2+1)-dimensional shallow water wave equation, Boussinesq equation, and the dispersive wave equations in shallow water serve as examples illustrating how compatibility leads quickly and easily to the determining equations for their nonclassical symmetries. (general)

The Cellular Distribution of RanGAP1 Is Regulated by CRM1-Mediated Nuclear Export in Mammalian Cells.

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Keith Cha

Full Text Available The Ran GTPase activating protein RanGAP1 plays an essential role in nuclear transport by stimulating RanGTP hydrolysis in the cytoplasmic compartment. In mammalian cells, unmodified RanGAP1 is predominantly cytoplasmic, whereas modification by small ubiquitin-related modifier protein (SUMO targets RanGAP1 to the cytoplasmic filaments of nuclear pore complex (NPC. Although RanGAP1 contains nine putative nuclear export signals and a nuclear localization signal, little is known if RanGAP1 shuttles between the nuclear and cytoplasmic compartments and how its primary localization in the cytoplasm and at the NPC is regulated. Here we show that inhibition of CRM1-mediated nuclear export using RNAi-knockdown of CRM1 and inactivation of CRM1 by leptomycin B (LMB results in nuclear accumulation of RanGAP1. LMB treatment induced a more robust redistribution of RanGAP1 from the cytoplasm to the nucleoplasm compared to CRM1 RNAi and also uniquely triggered a decrease or loss of RanGAP1 localization at the NPC, suggesting that LMB treatment is more effective in inhibiting CRM1-mediated nuclear export of RanGAP1. Our time-course analysis of LMB treatment reveals that the NPC-associated RanGAP1 is much more slowly redistributed to the nucleoplasm than the cytoplasmic RanGAP1. Furthermore, LMB-induced nuclear accumulation of RanGAP1 is positively correlated with an increase in levels of SUMO-modified RanGAP1, suggesting that SUMOylation of RanGAP1 may mainly take place in the nucleoplasm. Lastly, we demonstrate that the nuclear localization signal at the C-terminus of RanGAP1 is required for its nuclear accumulation in cells treated with LMB. Taken together, our results elucidate that RanGAP1 is actively transported between the nuclear and cytoplasmic compartments, and that the cytoplasmic and NPC localization of RanGAP1 is dependent on CRM1-mediated nuclear export.

Tuning crystallization pathways through sequence engineering of biomimetic polymers

Science.gov (United States)

Ma, Xiang; Zhang, Shuai; Jiao, Fang; Newcomb, Christina J.; Zhang, Yuliang; Prakash, Arushi; Liao, Zhihao; Baer, Marcel D.; Mundy, Christopher J.; Pfaendtner, James; Noy, Aleksandr; Chen, Chun-Long; de Yoreo, James J.

2017-07-01

Two-step nucleation pathways in which disordered, amorphous, or dense liquid states precede the appearance of crystalline phases have been reported for a wide range of materials, but the dynamics of such pathways are poorly understood. Moreover, whether these pathways are general features of crystallizing systems or a consequence of system-specific structural details that select for direct versus two-step processes is unknown. Using atomic force microscopy to directly observe crystallization of sequence-defined polymers, we show that crystallization pathways are indeed sequence dependent. When a short hydrophobic region is added to a sequence that directly forms crystalline particles, crystallization instead follows a two-step pathway that begins with the creation of disordered clusters of 10-20 molecules and is characterized by highly non-linear crystallization kinetics in which clusters transform into ordered structures that then enter the growth phase. The results shed new light on non-classical crystallization mechanisms and have implications for the design of self-assembling polymer systems.

Tuning crystallization pathways through sequence engineering of biomimetic polymers

Energy Technology Data Exchange (ETDEWEB)

Ma, Xiang; Zhang, Shuai; Jiao, Fang; Newcomb, Christina J.; Zhang, Yuliang; Prakash, Arushi; Liao, Zhihao; Baer, Marcel D.; Mundy, Christopher J.; Pfaendtner, James; Noy, Aleksandr; Chen, Chun-Long; De Yoreo, James J.

2017-04-17

Two-step nucleation pathways in which disordered, amorphous, or dense liquid states precede appearance of crystalline phases have been reported for a wide range of materials, but the dynamics of such pathways are poorly understood. Moreover, whether these pathways are general features of crystallizing systems or a consequence of system-specific structural details that select for direct vs two-step processes is unknown. Using atomic force microscopy to directly observe crystallization of sequence-defined polymers, we show that crystallization pathways are indeed sequence dependent. When a short hydrophobic region is added to a sequence that directly forms crystalline particles, crystallization instead follows a two-step pathway that begins with creation of disordered clusters of 10-20 molecules and is characterized by highly non-linear crystallization kinetics in which clusters transform into ordered structures that then enter the growth phase. The results shed new light on non-classical crystallization mechanisms and have implications for design of self-assembling polymer systems.

Equilibration and nonclassicality of a double-well potential.

Science.gov (United States)

Campbell, Steve; De Chiara, Gabriele; Paternostro, Mauro

2016-01-29

A double well loaded with bosonic atoms represents an ideal candidate to simulate some of the most interesting aspects in the phenomenology of thermalisation and equilibration. Here we report an exhaustive analysis of the dynamics and steady state properties of such a system locally in contact with different temperature reservoirs. We show that thermalisation only occurs 'accidentally'. We further examine the nonclassical features and energy fluxes implied by the dynamics of the double-well system, thus exploring its finite-time thermodynamics in relation to the settlement of nonclassical correlations between the wells.

Quantitative characterization of non-classic polarization of cations on clay aggregate stability.

Directory of Open Access Journals (Sweden)

Feinan Hu

Full Text Available Soil particle interactions are strongly influenced by the concentration, valence and ion species and the pH of the bulk solution, which will also affect aggregate stability and particle transport. In this study, we investigated clay aggregate stability in the presence of different alkali ions (Li+, Na+, K+, and Cs+ at concentrations from10-5 to 10-1 mol L-1. Strong specific ion effects on clay aggregate stability were observed, and showed the order Cs+>K+>Na+>Li+. We found that it was not the effects of ion size, hydration, and dispersion forces in the cation-surface interactions but strong non-classic polarization of adsorbed cations that resulted in these specific effects. In this study, the non-classic dipole moments of each cation species resulting from the non-classic polarization were estimated. By comparing non-classic dipole moments with classic values, the observed dipole moments of adsorbed cations were up to 104 times larger than the classic values for the same cation. The observed non-classic dipole moments sharply increased with decreasing electrolyte concentration. We conclude that strong non-classic polarization could significantly suppress the thickness of the diffuse layer, thereby weakening the electric field near the clay surface and resulting in improved clay aggregate stability. Even though we only demonstrated specific ion effects on aggregate stability with several alkali ions, our results indicate that these effects could be universally important in soil aggregate stability.

Quantitative Characterization of Non-Classic Polarization of Cations on Clay Aggregate Stability

Science.gov (United States)

Hu, Feinan; Li, Hang; Liu, Xinmin; Li, Song; Ding, Wuquan; Xu, Chenyang; Li, Yue; Zhu, Longhui

2015-01-01

Soil particle interactions are strongly influenced by the concentration, valence and ion species and the pH of the bulk solution, which will also affect aggregate stability and particle transport. In this study, we investigated clay aggregate stability in the presence of different alkali ions (Li+, Na+, K+, and Cs+) at concentrations from10−5 to 10−1 mol L−1. Strong specific ion effects on clay aggregate stability were observed, and showed the order Cs+>K+>Na+>Li+. We found that it was not the effects of ion size, hydration, and dispersion forces in the cation–surface interactions but strong non-classic polarization of adsorbed cations that resulted in these specific effects. In this study, the non-classic dipole moments of each cation species resulting from the non-classic polarization were estimated. By comparing non-classic dipole moments with classic values, the observed dipole moments of adsorbed cations were up to 104 times larger than the classic values for the same cation. The observed non-classic dipole moments sharply increased with decreasing electrolyte concentration. We conclude that strong non-classic polarization could significantly suppress the thickness of the diffuse layer, thereby weakening the electric field near the clay surface and resulting in improved clay aggregate stability. Even though we only demonstrated specific ion effects on aggregate stability with several alkali ions, our results indicate that these effects could be universally important in soil aggregate stability. PMID:25874864

A classical view on nonclassical nucleation.

Science.gov (United States)

Smeets, Paul J M; Finney, Aaron R; Habraken, Wouter J E M; Nudelman, Fabio; Friedrich, Heiner; Laven, Jozua; De Yoreo, James J; Rodger, P Mark; Sommerdijk, Nico A J M

2017-09-19

Understanding and controlling nucleation is important for many crystallization applications. Calcium carbonate (CaCO 3 ) is often used as a model system to investigate nucleation mechanisms. Despite its great importance in geology, biology, and many industrial applications, CaCO 3 nucleation is still a topic of intense discussion, with new pathways for its growth from ions in solution proposed in recent years. These new pathways include the so-called nonclassical nucleation mechanism via the assembly of thermodynamically stable prenucleation clusters, as well as the formation of a dense liquid precursor phase via liquid-liquid phase separation. Here, we present results from a combined experimental and computational investigation on the precipitation of CaCO 3 in dilute aqueous solutions. We propose that a dense liquid phase (containing 4-7 H 2 O per CaCO 3 unit) forms in supersaturated solutions through the association of ions and ion pairs without significant participation of larger ion clusters. This liquid acts as the precursor for the formation of solid CaCO 3 in the form of vaterite, which grows via a net transfer of ions from solution according to z Ca 2+ + z CO 3 2- → z CaCO 3 The results show that all steps in this process can be explained according to classical concepts of crystal nucleation and growth, and that long-standing physical concepts of nucleation can describe multistep, multiphase growth mechanisms.

Surfactant enhanced non-classical extraction

International Nuclear Information System (INIS)

Szymanowski, J.

2000-01-01

Surfactant enhanced non-classical extractions are presented and discussed. They include micellar enhanced ultrafiltration and cloud point extraction. The ideas of the processes are given and the main features are presented. They are compared to the classical solvent extraction. The fundamental of micellar solutions and their solubilisation abilities are also discussed. (author)

Surfactant enhanced non-classical extraction

International Nuclear Information System (INIS)

Szymanowski, J.

1999-01-01

Surfactant enhanced non-classical extractions are presented and discussed. They include micellar enhanced ultrafiltration and cloud point extraction. The ideas of the processes are given and the main features are presented. They are compared to the classical solvent extraction. The fundamental of micellar solutions and their solubilization abilities are also discussed. (author)

Activation of Ran GTPase by a Legionella effector promotes microtubule polymerization, pathogen vacuole motility and infection.

Directory of Open Access Journals (Sweden)

Eva Rothmeier

2013-09-01

Full Text Available The causative agent of Legionnaires' disease, Legionella pneumophila, uses the Icm/Dot type IV secretion system (T4SS to form in phagocytes a distinct "Legionella-containing vacuole" (LCV, which intercepts endosomal and secretory vesicle trafficking. Proteomics revealed the presence of the small GTPase Ran and its effector RanBP1 on purified LCVs. Here we validate that Ran and RanBP1 localize to LCVs and promote intracellular growth of L. pneumophila. Moreover, the L. pneumophila protein LegG1, which contains putative RCC1 Ran guanine nucleotide exchange factor (GEF domains, accumulates on LCVs in an Icm/Dot-dependent manner. L. pneumophila wild-type bacteria, but not strains lacking LegG1 or a functional Icm/Dot T4SS, activate Ran on LCVs, while purified LegG1 produces active Ran(GTP in cell lysates. L. pneumophila lacking legG1 is compromised for intracellular growth in macrophages and amoebae, yet is as cytotoxic as the wild-type strain. A downstream effect of LegG1 is to stabilize microtubules, as revealed by conventional and stimulated emission depletion (STED fluorescence microscopy, subcellular fractionation and Western blot, or by microbial microinjection through the T3SS of a Yersinia strain lacking endogenous effectors. Real-time fluorescence imaging indicates that LCVs harboring wild-type L. pneumophila rapidly move along microtubules, while LCVs harboring ΔlegG1 mutant bacteria are stalled. Together, our results demonstrate that Ran activation and RanBP1 promote LCV formation, and the Icm/Dot substrate LegG1 functions as a bacterial Ran activator, which localizes to LCVs and promotes microtubule stabilization, LCV motility as well as intracellular replication of L. pneumophila.

Activation of Ran GTPase by a Legionella Effector Promotes Microtubule Polymerization, Pathogen Vacuole Motility and Infection

Science.gov (United States)

Rothmeier, Eva; Pfaffinger, Gudrun; Hoffmann, Christine; Harrison, Christopher F.; Grabmayr, Heinrich; Repnik, Urska; Hannemann, Mandy; Wölke, Stefan; Bausch, Andreas; Griffiths, Gareth; Müller-Taubenberger, Annette; Itzen, Aymelt; Hilbi, Hubert

2013-01-01

The causative agent of Legionnaires' disease, Legionella pneumophila, uses the Icm/Dot type IV secretion system (T4SS) to form in phagocytes a distinct “Legionella-containing vacuole” (LCV), which intercepts endosomal and secretory vesicle trafficking. Proteomics revealed the presence of the small GTPase Ran and its effector RanBP1 on purified LCVs. Here we validate that Ran and RanBP1 localize to LCVs and promote intracellular growth of L. pneumophila. Moreover, the L. pneumophila protein LegG1, which contains putative RCC1 Ran guanine nucleotide exchange factor (GEF) domains, accumulates on LCVs in an Icm/Dot-dependent manner. L. pneumophila wild-type bacteria, but not strains lacking LegG1 or a functional Icm/Dot T4SS, activate Ran on LCVs, while purified LegG1 produces active Ran(GTP) in cell lysates. L. pneumophila lacking legG1 is compromised for intracellular growth in macrophages and amoebae, yet is as cytotoxic as the wild-type strain. A downstream effect of LegG1 is to stabilize microtubules, as revealed by conventional and stimulated emission depletion (STED) fluorescence microscopy, subcellular fractionation and Western blot, or by microbial microinjection through the T3SS of a Yersinia strain lacking endogenous effectors. Real-time fluorescence imaging indicates that LCVs harboring wild-type L. pneumophila rapidly move along microtubules, while LCVs harboring ΔlegG1 mutant bacteria are stalled. Together, our results demonstrate that Ran activation and RanBP1 promote LCV formation, and the Icm/Dot substrate LegG1 functions as a bacterial Ran activator, which localizes to LCVs and promotes microtubule stabilization, LCV motility as well as intracellular replication of L. pneumophila. PMID:24068924

Tackling complex turbulent flows with transient RANS

NARCIS (Netherlands)

Kenjeres, S.; Hanjalic, K.

2009-01-01

This article reviews some recent applications of the transient-Reynoldsaveraged Navier–Stokes (T-RANS) approach in simulating complex turbulent flows dominated by externally imposed body forces, primarily by thermal buoyancy and the Lorentz force. The T-RANS aims at numerical resolving unsteady

Optical nonclassicality test based on third-order intensity correlations

Science.gov (United States)

Rigovacca, L.; Kolthammer, W. S.; Di Franco, C.; Kim, M. S.

2018-03-01

We develop a nonclassicality criterion for the interference of three delayed, but otherwise identical, light fields in a three-mode Bell interferometer. We do so by comparing the prediction of quantum mechanics with those of a classical framework in which independent sources emit electric fields with random phases. In particular, we evaluate third-order correlations among output intensities as a function of the delays, and show how the presence of a correlation revival for small delays cannot be explained by the classical model of light. The observation of a revival is thus a nonclassicality signature, which can be achieved only by sources with a photon-number statistics that is highly sub-Poissonian. Our analysis provides strong evidence for the nonclassicality of the experiment discussed by Menssen et al. [Phys. Rev. Lett. 118, 153603 (2017), 10.1103/PhysRevLett.118.153603], and shows how a collective "triad" phase affects the interference of any three or more light fields, irrespective of their quantum or classical character.

Zonal PANS: evaluation of different treatments of the RANS-LES interface

Science.gov (United States)

Davidson, L.

2016-03-01

The partially Reynolds-averaged Navier-Stokes (PANS) model can be used to simulate turbulent flows either as RANS, large eddy simulation (LES) or DNS. Its main parameter is fk whose physical meaning is the ratio of the modelled to the total turbulent kinetic energy. In RANS fk = 1, in DNS fk = 0 and in LES fk takes values between 0 and 1. Three different ways of prescribing fk are evaluated for decaying grid turbulence and fully developed channel flow: fk = 0.4, fk = k3/2tot/ɛ and, from its definition, fk = k/ktot where ktot is the sum of the modelled, k, and resolved, kres, turbulent kinetic energy. It is found that the fk = 0.4 gives the best results. In Girimaji and Wallin, a method was proposed to include the effect of the gradient of fk. This approach is used at RANS- LES interface in the present study. Four different interface models are evaluated in fully developed channel flow and embedded LES of channel flow: in both cases, PANS is used as a zonal model with fk = 1 in the unsteady RANS (URANS) region and fk = 0.4 in the LES region. In fully developed channel flow, the RANS- LES interface is parallel to the wall (horizontal) and in embedded LES, it is parallel to the inlet (vertical). The importance of the location of the horizontal interface in fully developed channel flow is also investigated. It is found that the location - and the choice of the treatment at the interface - may be critical at low Reynolds number or if the interface is placed too close to the wall. The reason is that the modelled turbulent shear stress at the interface is large and hence the relative strength of the resolved turbulence is small. In RANS, the turbulent viscosity - and consequently also the modelled Reynolds shear stress - is only weakly dependent on Reynolds number. It is found in the present work that it also applies in the URANS region.

Higher-order RANS turbulence models for separated flows

Data.gov (United States)

National Aeronautics and Space Administration — Higher-order Reynolds-averaged Navier-Stokes (RANS) models are developed to overcome the shortcomings of second-moment RANS models in predicting separated flows....

The Essence of Nonclassicality: Non-Vanishing Signal Deficit

Science.gov (United States)

Aravinda, S.; Srikanth, R.

2015-12-01

Nonclassical properties of correlations- like unpredictability, no-cloning and uncertainty- are known to follow from two assumptions: nonlocality and no-signaling. For two-input-two-output correlations, we derive these properties from a single, unified assumption: namely, the excess of the communication cost over the signaling in the correlation. This is relevant to quantum temporal correlations, resources to simulate quantum correlations and extensions of quantum mechanics. We generalize in the context of such correlations the nonclassicality result for nonlocal-nonsignaling correlations (Masanes et al., Phys. Rev. A 73, 012112 (2006)) and the uncertainty bound on nonlocality (Oppenheim and Wehner, Science 330(6007), 1072 (2010)), when the no-signaling condition is relaxed.

Nonclassical Orthogonal Polynomials and Corresponding Quadratures

CERN Document Server

Fukuda, H; Alt, E O; Matveenko, A V

2004-01-01

We construct nonclassical orthogonal polynomials and calculate abscissas and weights of Gaussian quadrature for arbitrary weight and interval. The program is written by Mathematica and it works if moment integrals are given analytically. The result is a FORTRAN subroutine ready to utilize the quadrature.

Capacity Bounds on the Downlink of Symmetric, Multi-Relay, Single-Receiver C-RAN Networks

Directory of Open Access Journals (Sweden)

Shirin Saeedi Bidokhti

2017-11-01

Full Text Available The downlink of symmetric Cloud Radio Access Networks (C-RANs with multiple relays and a single receiver is studied. Lower and upper bounds are derived on the capacity. The lower bound is achieved by Marton’s coding, which facilitates dependence among the multiple-access channel inputs. The upper bound uses Ozarow’s technique to augment the system with an auxiliary random variable. The bounds are studied over scalar Gaussian C-RANs and are shown to meet and characterize the capacity for interesting regimes of operation.

Cloud RAN for Mobile Networks - a Technology Overview

OpenAIRE

Checko, Aleksandra; Christiansen, Henrik Lehrmann; Yan, Ying; Scolari, Lara; Kardaras, Georgios; Berger, Michael Stübert; Dittmann, Lars

2014-01-01

Cloud Radio Access Network (C-RAN) is a novel mobile network architecture which can address a number of challenges the operators face while trying to support growing end-user’s needs. The main idea behind C-RAN is to pool the Baseband Units (BBUs) from multiple base stations into centralized BBU Pool for statistical multiplexing gain, while shifting the burden to the high-speed wireline transmission of In-phase and Quadrature (IQ) data. C-RAN enables energy efficient network operation and pos...

Non-classical nonlinear feature extraction from standard resonance vibration data for damage detection.

Science.gov (United States)

Eiras, J N; Monzó, J; Payá, J; Kundu, T; Popovics, J S

2014-02-01

Dynamic non-classical nonlinear analyses show promise for improved damage diagnostics in materials that exhibit such structure at the mesoscale, such as concrete. In this study, nonlinear non-classical dynamic material behavior from standard vibration test data, using pristine and frost damaged cement mortar bar samples, is extracted and quantified. The procedure is robust and easy to apply. The results demonstrate that the extracted nonlinear non-classical parameters show expected sensitivity to internal damage and are more sensitive to changes owing to internal damage levels than standard linear vibration parameters.

Non-classical radiation transport in random media with fluctuating densities

International Nuclear Information System (INIS)

Dyuldya, S.V.; Bratchenko, M.I.

2012-01-01

The ensemble averaged propagation kernels of the non-classical radiation transport are studied by means of the proposed application of the stochastic differential equation random medium generators. It is shown that the non-classical transport is favored in long-correlated weakly fluctuating media. The developed kernel models have been implemented in GEANT4 and validated against the d ouble Monte Carlo m odeling of absorptions curves of disperse neutron absorbers and γ-albedos from a scatterer/absorber random mix

Significance of non-classical damping in seismic qualification of equipment and piping

Energy Technology Data Exchange (ETDEWEB)

Gupta, Abhinav, E-mail: agupta1@ncsu.edu; Bose, Mrinal K.

2017-06-15

Highlights: • Damping in coupled building-piping or building-equipment systems is nonlclassical. • Significance of nonclassical damping is illustrated. • Classical damping assumption can over predict or under predict response. • Significance of nonclassical damping increases for very light secondary systems. • Composite modal damping is another form of classical damping. - Abstract: This paper presents a discussion on the significance of non-classical damping in coupled primary-secondary systems such as building-equipment or building-piping. Closed-form expressions are used to illustrate that the effect of non-classical damping is significant in systems with tuned or nearly tuned uncoupled modes when the mass-interaction is sufficiently small. Further, simple primary-secondary systems are used to illustrate that composite modal damping is another form of classical damping for which the transformed damping matrix, obtained after pre- and post-multiplication of the damping matrix with the modal matrix, contains only diagonal terms. Both the composite and the classical damping give almost identical results that can be much different from the corresponding results for non-classical damping. Finally, it is shown that consideration of classical damping (ignoring the off-diagonal terms) can give excessively conservative results in nearly tuned primary-secondary systems. For perfectly tuned primary-secondary systems, however, classical damping can give responses that are much lower than what they should be.

Exponential attractors for a nonclassical diffusion equation

Directory of Open Access Journals (Sweden)

Qiaozhen Ma

2009-01-01

Full Text Available In this article, we prove the existence of exponential attractors for a nonclassical diffusion equation in ${H^{2}(Omega}cap{H}^{1}_{0}(Omega$ when the space dimension is less than 4.

Quantum nondemolition measurement with a nonclassical meter input and an electro-optic enhancement

DEFF Research Database (Denmark)

Andersen, Ulrik Lund; Buchler, B.C.; Bachor, H.A.

2002-01-01

Optical quantum nondemolition measurements are performed using a beamsplitter with a nonclassical meter input and a electro-optic feedforward loop. The nonclassical meter input is provided by a stable 4.5 dB amplitude squeezed source generated by an optical parametric amplifier. We show...

5th Symposium on Hybrid RANS-LES Methods

CERN Document Server

Haase, Werner; Peng, Shia-Hui; Schwamborn, Dieter

2015-01-01

This book gathers the proceedings of the Fifth Symposium on Hybrid RANS-LES Methods, which was held on March 19-21 in College Station, Texas, USA. The different chapters, written by leading experts, reports on the most recent developments in flow physics modelling, and gives a special emphasis to industrially relevant applications of hybrid RANS-LES methods and other turbulence-resolving modelling approaches. The book addresses academic researchers, graduate students, industrial engineers, as well as industrial R&D managers and consultants dealing with turbulence modelling, simulation and measurement, and with multidisciplinary applications of computational fluid dynamics (CFD), such as flow control, aero-acoustics, aero-elasticity and CFD-based multidisciplinary optimization. It discusses in particular advanced hybrid RANS-LES methods. Further topics include wall-modelled Large Eddy Simulation (WMLES) methods, embedded LES, and a comparison of the LES methods with both hybrid RANS-LES and URANS methods. ...

Evaluation of energy and cost savings in mobile Cloud RAN

DEFF Research Database (Denmark)

Checko, Aleksandra; Christiansen, Henrik Lehrmann; Berger, Michael Stübert

2013-01-01

, is sub optimal, comparing to a novel, cloud based architecture called Cloud Radio Access Network (C-RAN). In C-RAN a group of cells shares processing resources, and hence benefit from statistical multiplexing gain is expected. In this paper, the energy and cost savings in C-RAN are evaluated numerically...

Divergence en Route to Nonclassical Annonaceous Acetogenins

DEFF Research Database (Denmark)

Strand, Daniel; Norrby, Per-Ola; Rein, Tobias

2006-01-01

Syntheses of the nonclassical annonaceous acetogenins, pyranicin, and pyragonicin from common latestage intermediates are presented. The construction of key elements relies on asymmetric HWE reactions, including the desymmetrization of a meso-dialdehyde and a parallel kinetic resolution of a race...

Effect of dielectric medium on the nonclassical properties of nonlinear sphere coherent states

Directory of Open Access Journals (Sweden)

E Amooghorban

2014-04-01

Full Text Available In order to investigate the effect of a medium with dissipation and dispersion and also the curvature of the physical space on the properties of the incident quantum states, we use the quantization of electromagnetic field based on phenomenological approach to obtain input-output relations between radiations on both sides of dielectric slab. By using these relations the fidelity, the Wigner function, and also the quantum correlation of the outgoing state through dielectric slab are obtained for a situation in which the rightward incident state is a nonlinear coherent state on a sphere and the leftward incident state is a vacuum state. Here, the incident states are considered monochromatic and the modeling of the medium is given by the Lorentz' model. Accordingly, we study nonclassical properties of the output states such as the quantum entanglement. It will be observed that the nonclassical properties of the outgoing states depend strongly on the optical property of the medium and also on the curvature of the physical state.

The contribution of lexical access speed to RAN and reading

DEFF Research Database (Denmark)

Poulsen, Mads

and reading speed in the older age group was still strong after controlling for general speed of processing, but controlling for confrontation picture naming speed reduced the contribution of RAN to only marginally significant. Conclusions: We conclude that RAN-objects relationship with reading speed......Purpose: The study investigated why and when rapid automatised naming is a predictor of reading. Specifically, we tested the hypotheses that (1) RAN-objects predicts reading because it is a measure of lexical (e.g. phonological) access speed, but (2) that RAN only becomes a predictor of reading...... development once a certain level of phonological recoding proficiency has been reached. Method: Forty Danish students without reading difficulties were administered tests of reading speed and accuracy, phoneme awareness, RAN-objects, timed confrontation picture naming, and visio-motor reaction time...

Correspondence and canonicity in non-classical logic

NARCIS (Netherlands)

Sourabh, S.

2015-01-01

In this thesis we study correspondence and canonicity for non-classical logic using algebraic and order-topological methods. Correspondence theory is aimed at answering the question of how precisely modal, first-order, second-order languages interact and overlap in their shared semantic environment.

Local interaction simulation approach to modelling nonclassical, nonlinear elastic behavior in solids.

Science.gov (United States)

Scalerandi, Marco; Agostini, Valentina; Delsanto, Pier Paolo; Van Den Abeele, Koen; Johnson, Paul A

2003-06-01

Recent studies show that a broad category of materials share "nonclassical" nonlinear elastic behavior much different from "classical" (Landau-type) nonlinearity. Manifestations of "nonclassical" nonlinearity include stress-strain hysteresis and discrete memory in quasistatic experiments, and specific dependencies of the harmonic amplitudes with respect to the drive amplitude in dynamic wave experiments, which are remarkably different from those predicted by the classical theory. These materials have in common soft "bond" elements, where the elastic nonlinearity originates, contained in hard matter (e.g., a rock sample). The bond system normally comprises a small fraction of the total material volume, and can be localized (e.g., a crack in a solid) or distributed, as in a rock. In this paper a model is presented in which the soft elements are treated as hysteretic or reversible elastic units connected in a one-dimensional lattice to elastic elements (grains), which make up the hard matrix. Calculations are performed in the framework of the local interaction simulation approach (LISA). Experimental observations are well predicted by the model, which is now ready both for basic investigations about the physical origins of nonlinear elasticity and for applications to material damage diagnostics.

Cloud RAN for Mobile Networks - a Technology Overview

DEFF Research Database (Denmark)

Checko, Aleksandra; Christiansen, Henrik Lehrmann; Yan, Ying

2014-01-01

Cloud Radio Access Network (C-RAN) is a novel mobile network architecture which can address a number of challenges the operators face while trying to support growing end-user’s needs. The main idea behind C-RAN is to pool the Baseband Units (BBUs) from multiple base stations into centralized BBU...

A framework for resources allocation in virtualised C-RAN

DEFF Research Database (Denmark)

Al-Samman, Imad; Artuso, Matteo; Christiansen, Henrik Lehrmann

2016-01-01

the performance gains of different resource allocation schemes in legacy LTE air interface virtualization. Moreover Cloud — based mobile networks are anticipated to play a significant role for next generation mobile networks. This paper investigates the potential deployment benefits of a novel resource...... virtualization algorithm (Traffic Aware Joint Scheduling) in Cloud-RANs (C-RAN). Air interface resources are coordinated and allocated dynamically by a hypervisor among different virtual operators (VOs). Three distinctive schemes are proposed and evaluated against standard Round Robin (RR) C-RAN scheduling...

Envisioning Spectrum Management in Virtualised C-RAN

OpenAIRE

Al-Samman, Imad; Artuso, Matteo; Christiansen, Henrik Lehrmann; Doufexi, Angela; Beach, Mark

2017-01-01

Cloud Radio Access Network (C-RAN) has attracted a worldwide attention in both academia and industry. This network architecture re-forming has been considered as a potential solution to meet the increasing capacity demands for future mobile data traffic. In addition, Network Virtualisation is a promising technique for efficient resource utilisation. This paper proposes a customisable resource virtualisation algorithm for multi user data scheduling in a Long Term Evolution (LTE) C- RAN deploym...

Non-stationary pre-envelope covariances of non-classically damped systems

Science.gov (United States)

Muscolino, G.

1991-08-01

A new formulation is given to evaluate the stationary and non-stationary response of linear non-classically damped systems subjected to multi-correlated non-separable Gaussian input processes. This formulation is based on a new and more suitable definition of the impulse response function matrix for such systems. It is shown that, when using this definition, the stochastic response of non-classically damped systems involves the evaluation of quantities similar to those of classically damped ones. Furthermore, considerations about non-stationary cross-covariances, spectral moments and pre-envelope cross-covariances are presented for a monocorrelated input process.

Nonlinear Quantum Optical Springs and Their Nonclassical Properties

International Nuclear Information System (INIS)

Faghihi, M.J.; Tavassoly, M.K.

2011-01-01

The original idea of quantum optical spring arises from the requirement of quantization of the frequency of oscillations in the Hamiltonian of harmonic oscillator. This purpose is achieved by considering a spring whose constant (and so its frequency) depends on the quantum states of another system. Recently, it is realized that by the assumption of frequency modulation of ω to ω√1+μa † a the mentioned idea can be established. In the present paper, we generalize the approach of quantum optical spring with particular attention to the dependence of frequency to the intensity of radiation field that naturally observes in the nonlinear coherent states, from which we arrive at a physical system has been called by us as nonlinear quantum optical spring. Then, after the introduction of the generalized Hamiltonian of nonlinear quantum optical spring and it's solution, we will investigate the nonclassical properties of the obtained states. Specially, typical collapse and revival in the distribution functions and squeezing parameters, as particular quantum features, will be revealed. (electromagnetism, optics, acoustics, heat transfer, classical mechanics, and fluid dynamics)

Non-classicality criteria: Glauber-Sudarshan P function and Mandel ? parameter

Science.gov (United States)

Alexanian, Moorad

2018-01-01

We calculate exactly the quantum mechanical, temporal Wigner quasiprobability density for a single-mode, degenerate parametric amplifier for a system in the Gaussian state, viz., a displaced-squeezed thermal state. The Wigner function allows us to calculate the fluctuations in photon number and the quadrature variance. We contrast the difference between the non-classicality criteria, which is independent of the displacement parameter ?, based on the Glauber-Sudarshan quasiprobability distribution ? and the classical/non-classical behaviour of the Mandel ? parameter, which depends strongly on ?. We find a phase transition as a function of ? such that at the critical point ?, ?, as a function of ?, goes from strictly classical, for ?, to a mixed classical/non-classical behaviour, for ?.

Contour detection based on nonclassical receptive field inhibition

NARCIS (Netherlands)

Grigorescu, Cosmin; Petkov, Nicolai; Westenberg, Michel A.

We propose a biologically motivated computational step, called nonclassical receptive field (non-CRF) inhibition, more generally surround inhibition or suppression, to improve contour detection in machine vision. Non-CRF inhibition is exhibited by 80% of the orientation-selective neurons in the

Encephalomyocarditis virus Leader protein hinge domain is responsible for interactions with Ran GTPase

Energy Technology Data Exchange (ETDEWEB)

Bacot-Davis, Valjean R., E-mail: bacotdavis@wisc.edu [Institute for Molecular Virology, University of Wisconsin-Madison, R.M. Bock Laboratories, 1525 Linden Dr. Madison, WI 53706 (United States); Palmenberg, Ann C., E-mail: acpalmen@wisc.edu [Institute for Molecular Virology, University of Wisconsin-Madison, R.M. Bock Laboratories, 1525 Linden Dr. Madison, WI 53706 (United States); Department of Biochemistry, University of Wisconsin-Madison, R.M. Bock Laboratories, 1525 Linden Dr. Madison, WI 53706 (United States)

2013-08-15

Encephalomyocarditis virus (EMCV), a Cardiovirus, initiates its polyprotein with a short 67 amino acid Leader (L) sequence. The protein acts as a unique pathogenicity factor, with anti-host activities which include the triggering of nuclear pore complex hyperphosphorylation and direct binding inhibition of the active cellular transport protein, Ran GTPase. Chemical modifications and protein mutagenesis now map the Ran binding domain to the L hinge-linker region, and in particular, to amino acids 35–40. Large deletions affecting this region were shown previously to diminish Ran binding. New point mutations, especially K35Q, D37A and W40A, preserve the intact L structure, abolish Ran binding and are deficient for nucleoporin (Nup) hyperphosphorylation. Ran itself morphs through multiple configurations, but reacts most effectively with L when in the GDP format, preferably with an empty nucleotide binding pocket. Therefore, L:Ran binding, mediated by the linker-hinge, is a required step in L-induced nuclear transport inhibition. - Highlights: • The hinge domain provides critical residues in Cardiovirus L:Ran complex formation. • Leader prefers to bind Ran in a nucleotide free, GDP-conformation. • L-induced Nup62 phosphorylation is reduced with Ran-deficient binding mutations.

Experimental detection of nonclassical correlations in mixed-state quantum computation

International Nuclear Information System (INIS)

Passante, G.; Moussa, O.; Trottier, D. A.; Laflamme, R.

2011-01-01

We report on an experiment to detect nonclassical correlations in a highly mixed state. The correlations are characterized by the quantum discord and are observed using four qubits in a liquid-state nuclear magnetic resonance quantum information processor. The state analyzed is the output of a DQC1 computation, whose input is a single quantum bit accompanied by n maximally mixed qubits. This model of computation outperforms the best known classical algorithms and, although it contains vanishing entanglement, it is known to have quantum correlations characterized by the quantum discord. This experiment detects nonvanishing quantum discord, ensuring the existence of nonclassical correlations as measured by the quantum discord.

Hybrid RANS-LES using high order numerical methods

Science.gov (United States)

Henry de Frahan, Marc; Yellapantula, Shashank; Vijayakumar, Ganesh; Knaus, Robert; Sprague, Michael

2017-11-01

Understanding the impact of wind turbine wake dynamics on downstream turbines is particularly important for the design of efficient wind farms. Due to their tractable computational cost, hybrid RANS/LES models are an attractive framework for simulating separation flows such as the wake dynamics behind a wind turbine. High-order numerical methods can be computationally efficient and provide increased accuracy in simulating complex flows. In the context of LES, high-order numerical methods have shown some success in predictions of turbulent flows. However, the specifics of hybrid RANS-LES models, including the transition region between both modeling frameworks, pose unique challenges for high-order numerical methods. In this work, we study the effect of increasing the order of accuracy of the numerical scheme in simulations of canonical turbulent flows using RANS, LES, and hybrid RANS-LES models. We describe the interactions between filtering, model transition, and order of accuracy and their effect on turbulence quantities such as kinetic energy spectra, boundary layer evolution, and dissipation rate. This work was funded by the U.S. Department of Energy, Exascale Computing Project, under Contract No. DE-AC36-08-GO28308 with the National Renewable Energy Laboratory.

CLASSICAL AND NON-CLASSICAL PHILOSOPHICAL ANTHROPOLOGY: COMPARATIVE ANALYSIS

Directory of Open Access Journals (Sweden)

T. A. Kozlova

2018-01-01

Full Text Available Introduction: The goals and values of human life, the search for the meaning of human existence contain the potential for a meaningful, progressive development of philosophical and anthropological ideas at any time in history. One of the tasks of philosophical anthropology is the formation of the image of man, the choice of ways to achieve the ideal, the methods of comprehension and resolution of universal problems. The increasing processes of differentiation in science led to the formation of different views on the nature of man, to the distinction between classical and non-classical philosophical anthropology. А comparative analysis of these trends is given in this article.Materials and methods: The dialectical method is preferred in the question of research methodology, the hermeneutic and phenomenological approaches are used.Results: The development of philosophical anthropology correlates with the challenges of modernity. By tracking the trends of human change, philosophical anthropology changes the approach to the consideration of its main subject of research. The whole array of disciplines that study man comes to new discoveries, new theories, and philosophical anthropology changes its view of the vision, challenging the principles of classical philosophical anthropology.Classical philosophical anthropology elevates the biological nature of man to a pedestal, non-classical philosophical anthropology actualizes questions of language, culture, thinking, understanding, actualizes the hermeneutic and phenomenological approaches. The desire to understand a person in classical philosophical anthropology is based on the desire to fully reveal the biological mechanisms in a person. The perspective of treating a person in nonclassical philosophical anthropology is polyformen: man as a text, as a dreaming self, as an eternal transition. Non-classical philosophical anthropology, goes from the idea of identity to the idea of variability, from

Construction of classical and non-classical coherent photon states

International Nuclear Information System (INIS)

Honegger, Reinhard; Rieckers, Alfred

2001-01-01

It is well known that the diagonal matrix elements of all-order coherent states for the quantized electromagnetic field have to constitute a Poisson distribution with respect to the photon number. The present work gives first the summary of a constructive scheme, developed previously, which determines in terms of an auxiliary Hilbert space all possible off-diagonal elements for the all-order coherent density operators in Fock space and which identifies all extremal coherent states. In terms of this formalism it is then demonstrated that each pure classical coherent state is a uniformly phase locked (quantum) coherent superposition of number states. In a mixed classical coherent state the exponential of the locked phase is shown to be replaced by a rather arbitrary unitary operator in the auxiliary Hilbert space. On the other hand classes for density operators--and for their normally ordered characteristic functions--of non-classical coherent states are obtained, especially by rather weak perturbations of classical coherent states. These illustrate various forms of breaking the classical uniform phase locking and exhibit rather peculiar properties, such as asymmetric fluctuations for the quadrature phase operators. Several criteria for non-classicality are put forward and applied to the elaborated non-classical coherent states, providing counterexamples against too simple arguments for classicality. It is concluded that classicality is only a stable concept for coherent states with macroscopic intensity

Bipartite non-classical correlations for a lossy two connected qubit-cavity systems: trace distance discord and Bell's non-locality

Science.gov (United States)

Mohamed, Abdel-Baset A.

2018-04-01

In this paper, some non-classical correlations are investigated for bipartite partitions of two qubits trapped in two spatially separated cavities connected by an optical fiber. The results show that the trace distance discord and Bell's non-locality introduce other quantum correlations beyond the entanglement. Moreover, the correlation functions of the trace distance discord and the Bell's non-locality are very sensitive to the initial correlations, the coupling strengths, and the dissipation rates of the cavities. The fluctuations of the correlation functions between their initial values and gained (loss) values appear due to the unitary evolution of the system. These fluctuations depend on the chosen initial correlations between the two subsystems. The maximal violations of Bell's inequality occur when the logarithmic negativity and the trace distance discord reach certain values. It is shown that the robustness of the non-classical correlations, against the dissipation rates of the cavities, depends on the bipartite partitions reduced density matrices of the system, and is also greatly enhanced by choosing appropriate coupling strengths.

Formation of a Trimeric Xpo1-Ran[GTP]-Ded1 Exportin Complex Modulates ATPase and Helicase Activities of Ded1.

Directory of Open Access Journals (Sweden)

Glenn Hauk

Full Text Available The DEAD-box RNA helicase Ded1, which is essential in yeast and known as DDX3 in humans, shuttles between the nucleus and cytoplasm and takes part in several basic processes including RNA processing and translation. A key interacting partner of Ded1 is the exportin Xpo1, which together with the GTP-bound state of the small GTPase Ran, facilitates unidirectional transport of Ded1 out of the nucleus. Here we demonstrate that Xpo1 and Ran[GTP] together reduce the RNA-stimulated ATPase and helicase activities of Ded1. Binding and inhibition of Ded1 by Xpo1 depend on the affinity of the Ded1 nuclear export sequence (NES for Xpo1 and the presence of Ran[GTP]. Association with Xpo1/Ran[GTP] reduces RNA-stimulated ATPase activity of Ded1 by increasing the apparent KM for the RNA substrate. Despite the increased KM, the Ded1:Xpo1:Ran[GTP] ternary complex retains the ability to bind single stranded RNA, suggesting that Xpo1/Ran[GTP] may modulate the substrate specificity of Ded1. These results demonstrate that, in addition to transport, exportins such as Xpo1 also have the capability to alter enzymatic activities of their cargo.

Vortical structures and pressure pulsations in draft tube of a Francis-99 turbine at part load: RANS and hybrid RANS/LES analysis

International Nuclear Information System (INIS)

Gavrilov, A.A.; Sentyabov, A.V.; Dekterev, A.A.; Hanjalić, K.

2017-01-01

Highlights: • Simulations showed the formation of spiralling coherent vortices in the draft tube. • Both hybrid RANS-LES and Re-stress models reproduced well the measured fluctuations. • Re-stress model resolved the precessing vortex core and coherent spiralling vortices. - Abstract: Recognizing the limitations of the conventional linear-eddy-viscosity (LEVM) Reynolds-averaged Navier–Stokes (RANS) models to reproduce complex three-dimensional unsteady flows in hydraulic machinery, we performed a comparative assessment of a second-moment (Re-stress model, RSM) RANS closure and a hybrid RANS/LES method in capturing the flow and vortical structures in the draft tube of a Francis hydroturbine at off-design conditions. Considered is a case of part load (PL) at a flow rate of only 35% of the best efficiency point (BEP) characterised by multiple unsteady vortex systems. Despite some remaining uncertainties in generating the inflow conditions, both approaches reproduced reasonably well the measured mean velocity and the rms of its fluctuations, as well as the pressure spectrum with peaks detecting the precessing vortex core. In contrast to the common LEVMs, the Re-stress closure showed sufficient receptivity to intrinsic unsteadiness and reproduced well the overall flow and vortical patterns as well as the associated pressure pulsations in accord with the experiments. The hybrid RANS/LES method gave similar predictions as the RSM, but resolving a wider range of scales, which however, showed no significant effect on the dynamics of the dominant processing vortex core and the pressure pulsations.

Nonclassic Congenital Adrenal Hyperplasia

Directory of Open Access Journals (Sweden)

Selma Feldman Witchel

2010-01-01

Full Text Available Nonclassic congenital adrenal hyperplasia (NCAH due to P450c21 (21-hydroxylase deficiency is a common autosomal recessive disorder. This disorder is due to mutations in the CYP21A2 gene which is located at chromosome 6p21. The clinical features predominantly reflect androgen excess rather than adrenal insufficiency leading to an ascertainment bias favoring diagnosis in females. Treatment goals include normal linear growth velocity and “on-time” puberty in affected children. For adolescent and adult women, treatment goals include regularization of menses, prevention of progression of hirsutism, and fertility. This paper will review key aspects regarding pathophysiology, diagnosis, and treatment of NCAH.

Nonclassical lightstates in optical communication schemes

International Nuclear Information System (INIS)

Mattle, K. U.

1997-11-01

The present thesis is a result in theoretical and experimental work on quant information and quant communication. The first part describes a new high intense source for polarization entangled photon pairs. The high quality of the source is clearly demonstrated by violating a Bell-inequality in less than 5 minutes with 100 standard deviations. This new source is a genius tool for new experiments in the field of fundamental physics as well as applied physics. The next chapter shows an experimental implementation of an optical dense quantum coding scheme. The combination of Bell-state generation and analysis of this entangled states leads to a new nonclassical communication scheme, where the channel capacity is enhanced. A single two state photon can be used for coding and decoding 1.58 bit instead of 1 bit for classical two state systems. The following chapter discusses two photon interference effects for two independent light sources. In an experiment two independent fluorescence pulses show this kind of interference effects. The fifth chapter describes 3-photon interference effects. This nonclassical interference effect is the elementary process for the quantum teleportation scheme. In this scheme an unknown particle state is transmitted from A to B without sending the particle itself. (author)

Maximum Throughput in a C-RAN Cluster with Limited Fronthaul Capacity

OpenAIRE

Duan , Jialong; Lagrange , Xavier; Guilloud , Frédéric

2016-01-01

International audience; Centralized/Cloud Radio Access Network (C-RAN) is a promising future mobile network architecture which can ease the cooperation between different cells to manage interference. However, the feasibility of C-RAN is limited by the large bit rate requirement in the fronthaul. This paper study the maximum throughput of different transmission strategies in a C-RAN cluster with transmission power constraints and fronthaul capacity constraints. Both transmission strategies wit...

Tuning a RANS k-e model for jet-in-crossflow simulations.

Energy Technology Data Exchange (ETDEWEB)

Lefantzi, Sophia; Ray, Jaideep; Arunajatesan, Srinivasan; DeChant, Lawrence Justin

2013-09-01

We develop a novel calibration approach to address the problem of predictive ke RANS simulations of jet-incrossflow. Our approach is based on the hypothesis that predictive ke parameters can be obtained by estimating them from a strongly vortical flow, specifically, flow over a square cylinder. In this study, we estimate three ke parameters, C%CE%BC, Ce2 and Ce1 by fitting 2D RANS simulations to experimental data. We use polynomial surrogates of 2D RANS for this purpose. We conduct an ensemble of 2D RANS runs using samples of (C%CE%BC;Ce2;Ce1) and regress Reynolds stresses to the samples using a simple polynomial. We then use this surrogate of the 2D RANS model to infer a joint distribution for the ke parameters by solving a Bayesian inverse problem, conditioned on the experimental data. The calibrated (C%CE%BC;Ce2;Ce1) distribution is used to seed an ensemble of 3D jet-in-crossflow simulations. We compare the ensemble's predictions of the flowfield, at two planes, to PIV measurements and estimate the predictive skill of the calibrated 3D RANS model. We also compare it against 3D RANS predictions using the nominal (uncalibrated) values of (C%CE%BC;Ce2;Ce1), and find that calibration delivers a significant improvement to the predictive skill of the 3D RANS model. We repeat the calibration using surrogate models based on kriging and find that the calibration, based on these more accurate models, is not much better that those obtained with simple polynomial surrogates. We discuss the reasons for this rather surprising outcome.

Saccharomyces cerevisiae GTPase complex: Gtr1p-Gtr2p regulates cell-proliferation through Saccharomyces cerevisiae Ran-binding protein, Yrb2p

International Nuclear Information System (INIS)

Wang Yonggang; Nakashima, Nobutaka; Sekiguchi, Takeshi; Nishimoto, Takeharu

2005-01-01

A Gtr1p GTPase, the GDP mutant of which suppresses both temperature-sensitive mutants of Saccharomyces cerevisiae RanGEF/Prp20p and RanGAP/Rna1p, was presently found to interact with Yrb2p, the S. cerevisiae homologue of mammalian Ran-binding protein 3. Gtr1p bound the Ran-binding domain of Yrb2p. In contrast, Gtr2p, a partner of Gtr1p, did not bind Yrb2p, although it bound Gtr1p. A triple mutant: yrb2Δ gtr1Δ gtr2Δ was lethal, while a double mutant: gtr1Δ gtr2Δ survived well, indicating that Yrb2p protected cells from the killing effect of gtr1Δ gtr2Δ. Recombinant Gtr1p and Gtr2p were purified as a complex from Escherichia coli. The resulting Gtr1p-Gtr2p complex was comprised of an equal amount of Gtr1p and Gtr2p, which inhibited the Rna1p/Yrb2 dependent RanGAP activity. Thus, the Gtr1p-Gtr2p cycle was suggested to regulate the Ran cycle through Yrb2p

Assessment of unsteady-RANS approach against steady-RANS approach for predicting twin impinging jets in a cross-flow

Directory of Open Access Journals (Sweden)

Zhiyin Yang

2014-12-01

Full Text Available A complex flow field is created when a vertical/short take-off and landing aircraft is operating near ground. One major concern for this kind of aircraft in ground effect is the possibility of ingestion of hot gases from the jet engine exhausts back into the engine, known as hot gas ingestion, which can increase the intake air temperature and also reduce the oxygen content in the intake air, potentially leading to compressor stall, low combustion efficiency and causing a dramatic loss of lift. This flow field can be represented by the configuration of twin impinging jets in a cross-flow. Accurate prediction of this complicated flow field under the Reynolds averaged Navier–Stokes (RANS approach (current practise in industry is a great challenge as previous studies suggest that some important flow features cannot be captured by the Steady-RANS (SRANS approach even with a second-order Reynolds stress model (RSM. This paper presents a numerical study of this flow using the Unsteady-RANS (URANS approach with a RSM and the results clearly indicate that the URANS approach is superior than the SRANS approach but still the predictions of Reynolds stress are not accurate enough.

Knockdown of Ran GTPase expression inhibits the proliferation and migration of breast cancer cells.

Science.gov (United States)

Sheng, Chenyi; Qiu, Jian; Wang, Yingying; He, Zhixian; Wang, Hua; Wang, Qingqing; Huang, Yeqing; Zhu, Lianxin; Shi, Feng; Chen, Yingying; Xiong, Shiyao; Xu, Zhen; Ni, Qichao

2018-05-03

Breast cancer is the second leading cause of cancer‑associated mortality in women worldwide. Strong evidence has suggested that Ran, which is a small GTP binding protein involved in the transport of RNA and protein across the nucleus, may be a key cellular protein involved in the metastatic progression of cancer. The present study investigated Ran gene expression in breast cancer tissue samples obtained from 140 patients who had undergone surgical resection for breast cancer. Western blot analysis of Ran in breast cancer tissues and paired adjacent normal tissues showed that expression of Ran was significantly increased in breast cancer tissues. Immunohistochemistry analyses conducted on formalin‑fixed paraffin‑embedded breast cancer tissue sections revealed that Ran expression was associated with tumor histological grade, nerve invasion and metastasis, vascular metastasis and Ki‑67 expression (a marker of cell proliferation). Kaplan‑Meier survival analysis showed that increased Ran expression in patients with breast cancer was positively associated with a poor survival prognosis. Furthermore, in vitro experiments demonstrated that highly migratory MDA‑MB‑231 cancer cells treated with Ran‑si‑RNA (si‑Ran), which knocked down expression of Ran, exhibited decreased motility in trans‑well migration and wound healing assays. Cell cycle analysis of Ran knocked down MDA‑MB‑231 cells implicated Ran in cell cycle arrest and the inhibition of proliferation. Furthermore, a starvation and re‑feeding (CCK‑8) assay was performed, which indicated that Ran regulated breast cancer cell proliferation. Taken together, the results provide strong in vitro evidence of the involvement of Ran in the progression of breast cancer and suggest that it could have high potential as a therapeutic target and/or marker of disease.

Multinomial Bayesian learning for modeling classical and nonclassical receptive field properties.

Science.gov (United States)

Hosoya, Haruo

2012-08-01

We study the interplay of Bayesian inference and natural image learning in a hierarchical vision system, in relation to the response properties of early visual cortex. We particularly focus on a Bayesian network with multinomial variables that can represent discrete feature spaces similar to hypercolumns combining minicolumns, enforce sparsity of activation to learn efficient representations, and explain divisive normalization. We demonstrate that maximal-likelihood learning using sampling-based Bayesian inference gives rise to classical receptive field properties similar to V1 simple cells and V2 cells, while inference performed on the trained network yields nonclassical context-dependent response properties such as cross-orientation suppression and filling in. Comparison with known physiological properties reveals some qualitative and quantitative similarities.

Age-dependent alterations of monocyte subsets and monocyte-related chemokine pathways in healthy adults

Directory of Open Access Journals (Sweden)

Trautwein Christian

2010-06-01

Full Text Available Abstract Background Recent experimental approaches have unraveled essential migratory and functional differences of monocyte subpopulations in mice. In order to possibly translate these findings into human physiology and pathophysiology, human monocyte subsets need to be carefully revisited in health and disease. In analogy to murine studies, we hypothesized that human monocyte subsets dynamically change during ageing, potentially influencing their functionality and contributing to immunosenescence. Results Circulating monocyte subsets, surface marker and chemokine receptor expression were analyzed in 181 healthy volunteers (median age 42, range 18-88. Unlike the unaffected total leukocyte or total monocyte counts, non-classical CD14+CD16+ monocytes significantly increased with age, but displayed reduced HLA-DR and CX3CR1 surface expression in the elderly. Classical CD14++CD16- monocyte counts did not vary dependent on age. Serum MCP-1 (CCL2, but not MIP1α (CCL3, MIP1β (CCL4 or fractalkine (CX3CL1 concentrations increased with age. Monocyte-derived macrophages from old or young individuals did not differ with respect to cytokine release in vitro at steady state or upon LPS stimulation. Conclusions Our study demonstrates dynamic changes of circulating monocytes during ageing in humans. The expansion of the non-classical CD14+CD16+ subtype, alterations of surface protein and chemokine receptor expression as well as circulating monocyte-related chemokines possibly contribute to the preserved functionality of the monocyte pool throughout adulthood.

DMPD: Crosstalk among Jak-STAT, Toll-like receptor, and ITAM-dependent pathways inmacrophage activation. [Dynamic Macrophage Pathway CSML Database

Lifescience Database Archive (English)

Full Text Available 17502339 Crosstalk among Jak-STAT, Toll-like receptor, and ITAM-dependent pathways inmacrophage...May 14. (.png) (.svg) (.html) (.csml) Show Crosstalk among Jak-STAT, Toll-like receptor, and ITAM-dependent pathways inmacrophage...T, Toll-like receptor, and ITAM-dependent pathways inmacrophage activation. Authors Hu X, Chen J, Wang L, Iv

Power Optimization With BLER Constraint for Wireless Fronthauls in C-RAN

OpenAIRE

Vu, Thang Xuan; Nguyen, Thang Van; Quek, Tony Q.S.

2016-01-01

Cloud radio access network (C-RAN) is a novel architecture for future mobile networks to sustain the exponential traffic growth thanks to the exploitation of centralized processing. In C-RAN, one data processing center or baseband unit (BBU) communicates with users via distributed remote radio heads (RRHs), which are connected to the BBU via high capacity, low latency fronthaul links. In this letter, we study C-RAN with wireless fronthauls due to their flexibility in deployment and management...

Classical and nonclassical randomness in quantum measurements

International Nuclear Information System (INIS)

Farenick, Douglas; Plosker, Sarah; Smith, Jerrod

2011-01-01

The space POVM H (X) of positive operator-valued probability measures on the Borel sets of a compact (or even locally compact) Hausdorff space X with values in B(H), the algebra of linear operators acting on a d-dimensional Hilbert space H, is studied from the perspectives of classical and nonclassical convexity through a transform Γ that associates any positive operator-valued measure ν with a certain completely positive linear map Γ(ν) of the homogeneous C*-algebra C(X) x B(H) into B(H). This association is achieved by using an operator-valued integral in which nonclassical random variables (that is, operator-valued functions) are integrated with respect to positive operator-valued measures and which has the feature that the integral of a random quantum effect is itself a quantum effect. A left inverse Ω for Γ yields an integral representation, along the lines of the classical Riesz representation theorem for linear functionals on C(X), of certain (but not all) unital completely positive linear maps φ:C(X) x B(H)→B(H). The extremal and C*-extremal points of POVM H (X) are determined.

Assesment of Rhythm Disorders in Classical and Nonclassical Mitral Valve Prolapse.

Science.gov (United States)

Hodzic, Enisa

2018-02-01

Mitral Valve Prolapse (MVP) is the most common cardiac valve pathology of to day. Aim of article was to identify the types and frequency of potentially malignant arrhythmia and atrial brillation in patients with MVP, to determine the differences in these arrhythmias between classical and non-classical MVP, to evaluate the correlation of potentially malignant arrhythmia and atrial fibrillation with MVP with possible clinical complications of arrhythmogenic sudden cardiac death and potential risk of thromboembolic vascular incident. Article has retrospective-prospective analytical character and present observational study on 239 patients (120 with MVP (66 with classical and 54 with non-classical MVP), who had a subjective feeling of palpitations and/or pain in the chest, and/or episode of syncope, and did not have ischemic heart disease or another valve pathology) and 119 healthy patients in the control group. All patients were analyzed by 24-hour ECG Holter. Signifficant difference in all analyzed arrhythmias between classical MVP and control group (p MVP (p = 0.016). The potential risk of cardiac death and vascular incidence is signi cantly higher in classical MVP than in non-classical MVP, implying the need for routine ECG-Holter monitoring in their diagnosis for timely prevention of clinical arrhythmogenic complications.

Optimizing Cloud-RAN Deployments in Real-life Scenarios Using Microwave Radio

DEFF Research Database (Denmark)

Al-obaidi, Rami; Checko, Aleksandra; Holm, Henrik

2015-01-01

Cloud Radio Access Network (C-RAN) is a new architecture designed to be the candidate for enabling future mobile networks. However, it will be deployed only if it is economically viable. In this paper we investigate the technological options of C-RAN deployments. By using analytical methods we...... derive engineering guidelines for minimizing the CAPital EXpenditure (CAPEX) of C-RAN deployment. We show for which population density and span of BBU Pool coverage usage of Microwave Radio (MWR) links is viable. For larger scale deployment we recommend to divide the area into multiple BBU Pools....

Observational study of differences in head position for high notes in famous classical and non-classical male singers.

Science.gov (United States)

Amarante Andrade, Pedro; Švec, Jan G

2016-07-01

Differences in classical and non-classical singing are due primarily to aesthetic style requirements. The head position can affect the sound quality. This study aimed at comparing the head position for famous classical and non-classical male singers performing high notes. Images of 39 Western classical and 34 non-classical male singers during live performances were obtained from YouTube. Ten raters evaluated the frontal rotational head position (depression versus elevation) and transverse head position (retraction versus protraction) visually using a visual analogue scale. The results showed a significant difference for frontal rotational head position. Most non-classical singers in the sample elevated their heads for high notes while the classical singers were observed to keep it around the neutral position. This difference may be attributed to different singing techniques and phonatory system adjustments utilized by each group.

Performance Analysis of Several Functional Splits in C-RAN

OpenAIRE

Duan , Jialong; Lagrange , Xavier; Guilloud , Frédéric

2016-01-01

International audience; Centralized/Cloud Radio Access Network (C-RAN) is a promising future mobile network architecture, which can potentially increase the capacity of mobile network meanwhile reducing operators' cost. In standard C-RAN, frequency shifting is made in Remote Radio Heads (RRHs), which are close to the antennas. Signal processing and upper layers are made in Baseband Unit (BBU) pool for multiple base stations. However, this results in high burden on the optical transport networ...

In Vitro Characterization of the Two-Stage Non-Classical Reassembly Pathway of S-Layers

Directory of Open Access Journals (Sweden)

Andreas Breitwieser

2017-02-01

Full Text Available The recombinant bacterial surface layer (S-layer protein rSbpA of Lysinibacillus sphaericus CCM 2177 is an ideal model system to study non-classical nucleation and growth of protein crystals at surfaces since the recrystallization process may be separated into two distinct steps: (i adsorption of S-layer protein monomers on silicon surfaces is completed within 5 min and the amount of bound S-layer protein sufficient for the subsequent formation of a closed crystalline monolayer; (ii the recrystallization process is triggered—after washing away the unbound S-layer protein—by the addition of a CaCl2 containing buffer solution, and completed after approximately 2 h. The entire self-assembly process including the formation of amorphous clusters, the subsequent transformation into crystalline monomolecular arrays, and finally crystal growth into extended lattices was investigated by quartz crystal microbalance with dissipation (QCM-D and atomic force microscopy (AFM. Moreover, contact angle measurements showed that the surface properties of S-layers change from hydrophilic to hydrophobic as the crystallization proceeds. This two-step approach is new in basic and application driven S-layer research and, most likely, will have advantages for functionalizing surfaces (e.g., by spray-coating with tailor-made biological sensing layers.

Non-Classical C–H···X Hydrogen Bonding and Its Role in Asymmetric Organocatalysis

KAUST Repository

Ajitha, Manjaly John; Huang, Kuo-Wei

2016-01-01

Non-classical hydrogen bonds (NCHBs) have attracted significant interest in the past decade particularly because of their important role in asymmetric catalytic systems. These weak interactions (< 4 kcal/mol) offer much flexibility1 Introduction2 Hydrogen Bonds (HBs) and Non-Classical Hydrogen Bonds (NCHBs)3 Early Developments in NCHBs4 Selected Examples of NCHBs in Organic Transformations5 Recent Examples of NCHBs in Enantioselective Reactions6 Conclusions and Outlook

The proliferation marker pKi-67 organizes the nucleolus during the cell cycle depending on Ran and cyclin B.

Science.gov (United States)

Schmidt, Mirko H H; Broll, Rainer; Bruch, Hans-Peter; Bögler, Oliver; Duchrow, Michael

2003-01-01

The proliferation marker pKi-67 ('Ki-67 antigen') is commonly used in clinical and research pathology to detect proliferating cells, as it is only expressed during cell-cycle progression. Despite the fact that this antigen has been known for nearly two decades, there is still no adequate understanding of its function. This study has therefore identified proteins that interact with pKi-67, using a yeast two-hybrid system. A mammalian two-hybrid system and immunoprecipitation studies were used to verify these interactions. Among other cell-cycle regulatory proteins, two binding partners associated with the small GTPase Ran were identified. In addition, DNA-structural and nucleolus-associated proteins binding to pKi-67 were found. Moreover, it was demonstrated that the N-terminal domain of pKi-67 is capable of self-binding to its own repeat region encoded by exon 13. Since RanBP, a protein involved in the transport of macromolecules over the nuclear lamina, was found to be a binding partner, a possible effect of pKi-67 on the localization of cell-cycle regulatory proteins was proposed. To test this hypothesis, a tetracycline-responsive gene expression system was used to induce the pKi-67 fragments previously used for the two-hybrid screens in HeLa cells. Subsequent immunostaining revealed the translocation of cyclin B1 from cytoplasm to nucleoli in response to this expression. It is suggested that pKi-67 is a Ran-associated protein with a role in the disintegration and reformation of the nucleolus and thereby in entry into and exit from the M-phase. Copyright 2002 John Wiley & Sons, Ltd.

Nonclassicality threshold for the three-qubit Greenberger-Horne-Zeilinger state

International Nuclear Information System (INIS)

Vertesi, Tamas; Pal, Karoly F.

2011-01-01

The nonclassical properties of the noisy three-qubit Greenberger-Horne-Zeilinger (GHZ) states, ρ v =v|GHZ> v is nonclassical for the parameter range 1/2< v≤1. It has been posed whether additional settings would allow to lower the threshold visibility. Here we report on Bell inequalities giving a threshold value smaller than v=1/2. This rules out the possibility of a local hidden variable model in the limit of v=1/2. In particular, the lowest threshold visibility we found is v=0.496 057, attainable with 5x5x5 settings, whereas the most economical one in number of settings corresponds to 3x3x4 settings. The method which enabled us to obtain these results, and in particular the about 10 000 tight Bell inequalities giving v<1/2, are also discussed in detail.

Non-classical continuum mechanics a dictionary

CERN Document Server

Maugin, Gérard A

2017-01-01

This dictionary offers clear and reliable explanations of over 100 keywords covering the entire field of non-classical continuum mechanics and generalized mechanics, including the theory of elasticity, heat conduction, thermodynamic and electromagnetic continua, as well as applied mathematics. Every entry includes the historical background and the underlying theory, basic equations and typical applications. The reference list for each entry provides a link to the original articles and the most important in-depth theoretical works. Last but not least, every entry is followed by a cross-reference to other related subject entries in the dictionary.

AVHRR GAC SST Reanalysis Version 1 (RAN1

Directory of Open Access Journals (Sweden)

Alexander Ignatov

2016-04-01

Full Text Available In response to its users’ needs, the National Oceanic and Atmospheric Administration (NOAA initiated reanalysis (RAN of the Advanced Very High Resolution Radiometer (AVHRR Global Area Coverage (GAC; 4 km sea surface temperature (SST data employing its Advanced Clear Sky Processor for Oceans (ACSPO retrieval system. Initially, AVHRR/3 data from five NOAA and two Metop satellites from 2002 to 2015 have been reprocessed. The derived SSTs have been matched up with two reference SSTs—the quality controlled in situ SSTs from the NOAA in situ Quality Monitor (iQuam and the Canadian Meteorological Centre (CMC L4 SST analysis—and analyzed in the NOAA SST Quality Monitor (SQUAM online system. The corresponding clear-sky ocean brightness temperatures (BT in AVHRR bands 3b, 4 and 5 (centered at 3.7, 11, and 12 µm, respectively have been compared with the Community Radiative Transfer Model simulations in another NOAA online system, Monitoring of Infrared Clear-sky Radiances over Ocean for SST (MICROS. For some AVHRRs, the time series of “AVHRR minus reference” SSTs and “observed minus model” BTs are unstable and inconsistent, with artifacts in the SSTs and BTs strongly correlated. In the official “Reanalysis version 1” (RAN1, data from only five platforms—two midmorning (NOAA-17 and Metop-A and three afternoon (NOAA-16, -18 and -19—were included during the most stable periods of their operations. The stability of the SST time series was further improved using variable regression SST coefficients, similarly to how it was done in the NOAA/NASA Pathfinder version 5.2 (PFV5.2 dataset. For data assimilation applications, especially those blending satellite and in situ SSTs, we recommend bias-correcting the RAN1 SSTs using the newly developed sensor-specific error statistics (SSES, which are reported in the product files. Relative performance of RAN1 and PFV5.2 SSTs is discussed. Work is underway to improve the calibration of AVHRR/3s and

Nonclassicality of Photon-Added Displaced Thermal State via Quantum Phase-Space Distributions

Science.gov (United States)

Zhang, Ran; Meng, Xiang-Guo; Du, Chuan-Xun; Wang, Ji-Suo

2018-02-01

We introduce a new kind of nonclassical mixed state generated by adding arbitrary photons to a displaced thermal state, i.e., the photon-added displaced thermal state (PADTS), and obtain the normalization factor, which is simply related to two-variable Hermite polynomials. We also discuss the nonclassicality of the PADTS by considering quantum phase-space distributions. The results indicate that the value of the photon count statistics is maximum when the number of detected photons is equal to the number of added photons, and that the photon-added operation has a similar modulation effect with increasing displacement. Moreover, the negative volume of the Wigner function for the PADTS takes a maximal value for a specific photon-added number.

Non-classical Signature of Parametric Fluorescence and its Application in Metrology

Directory of Open Access Journals (Sweden)

Hamar M.

2014-08-01

Full Text Available The article provides a short theoretical background of what the non-classical light means. We applied the criterion for the existence of non-classical effects derived by C.T. Lee on parametric fluorescence. The criterion was originally derived for the study of two light beams with one mode per beam. We checked if the criterion is still working for two multimode beams of parametric down-conversion through numerical simulations. The theoretical results were tested by measurement of photon number statistics of twin beams emitted by nonlinear BBO crystal pumped by intense femtoseconds UV pulse. We used ICCD camera as the detector of photons in both beams. It appears that the criterion can be used for the measurement of the quantum efficiencies of the ICCD cameras.

Symplectic tomography of nonclassical states of trapped ion

International Nuclear Information System (INIS)

Man'ko, O.

1996-03-01

The marginal distribution for two types of nonclassical states of trapped ion - for squeezed and correlated states and for squeezed even and odd coherent states (squeezed Schroedinger cat states) is studied. The obtained marginal distribution for the two types of states is shown to satisfy classical dynamical equation equivalent to standard quantum evolution equation for density matrix (wave function) derived in symplectic tomography scheme. (author). 20 refs

Why aortic elasticity differs among classical and non-classical mitral valve prolapsed?

Science.gov (United States)

Unlu, Murat; Demirkol, Sait; Aparci, Mustafa; Arslan, Zekeriya; Balta, Sevket; Dogan, Umuttan; Kilicarslan, Baris; Ozeke, Ozcan; Celik, Turgay; Iyisoy, Atila

2014-01-01

Mitral valve prolapse (MVP) is the most common valvular heart disease and characterized by the displacement of an abnormally thickened mitral valve leaflet into the left atrium during systole. There are two types of MVP, broadly classified as classic (thickness ≥5 mm) and non-classic (thickness elastic properties of the aorta in young male patients with classical and non-classical MVP. In the present study, 63 young adult males (mean age: 22.7 ± 4.2) were included. Patients were divided into classic MVP (n = 27) and non-classic MVP (n = 36) groups. Aortic strain, aortic distensibility and aortic stiffness index were calculated by using aortic diameters obtained by echocardiography and blood pressures measured by sphygmomanometer. There was no significant difference between the groups in terms of age, body mass index, left ventricular mass and ejection fraction. When comparing the MVP group it was found that aortic strain and aortic distensibility were increased (p = 0.0027, p = 0.016, respectively) whereas the aortic stiffness index was decreased (p = 0.06) in the classical MVP group. We concluded that the elastic properties of the aorta is increased in patients with classic MVP. Further large scale studies should be performed to understand of morphological and physiological properties of the aorta in patients with MVP.

Envisioning Spectrum Management in Virtualised C-RAN

DEFF Research Database (Denmark)

Al-Samman, Imad; Artuso, Matteo; Christiansen, Henrik Lehrmann

2017-01-01

Cloud Radio Access Network (C-RAN) has attracted a worldwide attention in both academia and industry. This network architecture re-forming has been considered as a potential solution to meet the increasing capacity demands for future mobile data traffic. In addition, Network Virtualisation...... is a promising technique for efficient resource utilisation. This paper proposes a customisable resource virtualisation algorithm for multi user data scheduling in a Long Term Evolution (LTE) C- RAN deployment. The algorithm is based on the hypervisor specific assignment of air resources allocation between...... the virtual operators (VOs) dynamically, based on either joint scheduling or per cell schemes. The objective is to improve the resource allocation mechanism based on traffic conditions and a database of pre-defined services priorities. Two distinctive scenarios are considered and evaluated against standard...

The down-stream effects of mannan-induced lectin complement pathway activation depend quantitatively on alternative pathway amplification

DEFF Research Database (Denmark)

Harboe, Morten; Garred, Peter; Karlstrøm, Ellen

2009-01-01

Complement activation plays an important role in human pathophysiology. The effect of classical pathway activation is largely dependent on alternative pathway (AP) amplification, whereas the role of AP for the down-stream effect of mannan-induced lectin pathway (LP) activation is poorly understood...... that AP amplification is quantitatively responsible for the final effect of initial specific LP activation. TCC generation on the solid phase was distinctly but less inhibited by anti-fD. C2 bypass of the LP pathway could be demonstrated, and AP amplification was also essential during C2 bypass in LP...... as shown by complete inhibition of TCC generation in C2-deficient serum by anti-fD and anti-properdin antibodies. In conclusion, the down-stream effect of LP activation depends strongly on AP amplification in normal human serum and in the C2 bypass pathway....

Energy Efficient Precoding C-RAN Downlink with Compression at Fronthaul

OpenAIRE

Nguyen, Kien-Giang; Vu, Quang-Doanh; Juntti, Markku; Tran, Le-Nam

2017-01-01

This paper considers a downlink transmission of cloud radio access network (C-RAN) in which precoded baseband signals at a common baseband unit are compressed before being forwarded to radio units (RUs) through limited fronthaul capacity links. We investigate the joint design of precoding, multivariate compression and RU-user selection which maximizes the energy efficiency of downlink C-RAN networks. The considered problem is inherently a rank-constrained mixed Boolean nonconvex program for w...

Nonclassicality characterization in photon statistics based on binary-response single-photon detection

International Nuclear Information System (INIS)

Guo Yanqiang; Yang Rongcan; Li Gang; Zhang Pengfei; Zhang Yuchi; Wang Junmin; Zhang Tiancai

2011-01-01

By employing multiple conventional single-photon counting modules (SPCMs), which are binary-response detectors, instead of photon number resolving detectors, the nonclassicality criteria are investigated for various quantum states. The bounds of the criteria are derived from a system based on three or four SPCMs. The overall efficiency and background are both taken into account. The results of experiments with thermal and coherent light agree with the theoretical analysis. Compared with photon number resolving detectors, the use of a Hanbury Brown-Twiss-like scheme with multiple SPCMs is even better for revealing the nonclassicality of the fields, and the efficiency requirements are not so stringent. Some proposals are presented which can improve the detection performance with binary-response SPCMs for different quantum states.

Determination of Scaled Wind Turbine Rotor Characteristics from Three Dimensional RANS Calculations

International Nuclear Information System (INIS)

Burmester, S; Gueydon, S; Make, M

2016-01-01

Previous studies have shown the importance of 3D effects when calculating the performance characteristics of a scaled down turbine rotor [1-4]. In this paper the results of 3D RANS (Reynolds-Averaged Navier-Stokes) computations by Make and Vaz [1] are taken to calculate 2D lift and drag coefficients. These coefficients are assigned to FAST (Blade Element Momentum Theory (BEMT) tool from NREL) as input parameters. Then, the rotor characteristics (power and thrust coefficients) are calculated using BEMT. This coupling of RANS and BEMT was previously applied by other parties and is termed here the RANS-BEMT coupled approach. Here the approach is compared to measurements carried out in a wave basin at MARIN applying Froude scaled wind, and the direct 3D RANS computation. The data of both a model and full scale wind turbine are used for the validation and verification. The flow around a turbine blade at full scale has a more 2D character than the flow properties around a turbine blade at model scale (Make and Vaz [1]). Since BEMT assumes 2D flow behaviour, the results of the RANS-BEMT coupled approach agree better with the results of the CFD (Computational Fluid Dynamics) simulation at full- than at model-scale. (paper)

General and Specific Contributions of RAN to Reading and Arithmetic Fluency in First Graders: A Longitudinal Latent Variable Approach

Directory of Open Access Journals (Sweden)

Caroline Hornung

2017-10-01

Full Text Available In the present study, we opted for a longitudinal design and examined rapid automatized naming (RAN performance from two perspectives. In a first step, we examined the structure of RAN performance from a general cognitive perspective. We investigated whether rapid naming measures (e.g., digit RAN and color RAN reflect a mainly domain-general factor or domain-specific factors. In a second step, we examined how the best fitting RAN model was related to reading and arithmetic outcomes, assessed several months later. Finally in a third step we took a clinical perspective and investigated specific contributions of RAN measures to reading and arithmetic outcomes. While RAN has emerged as a promising predictor of reading, the relationship between RAN and arithmetic has been less examined in the past. Hundred and twenty-two first graders completed seven RAN tasks, each comprising visually familiar stimuli such as digits, vowels, consonants, dice, finger-numeral configurations, objects, and colors. Four months later the same children completed a range of reading and arithmetic tasks. From a general descriptive perspective, structural equation modeling supports a one-dimensional RAN factor in 6- to -7-year-old children. However, from a clinical perspective, our findings emphasize the specific contributions of RANs. Interestingly, alphanumeric RANs (i.e., vowel RAN were most promising when predicting reading skills and number-specific RANs (i.e., finger-numeral configuration RAN were most promising when predicting arithmetic fluency. The implications for clinical and educational practices will be discussed.

General and Specific Contributions of RAN to Reading and Arithmetic Fluency in First Graders: A Longitudinal Latent Variable Approach.

Science.gov (United States)

Hornung, Caroline; Martin, Romain; Fayol, Michel

2017-01-01

In the present study, we opted for a longitudinal design and examined rapid automatized naming (RAN) performance from two perspectives. In a first step, we examined the structure of RAN performance from a general cognitive perspective. We investigated whether rapid naming measures (e.g., digit RAN and color RAN) reflect a mainly domain-general factor or domain-specific factors. In a second step, we examined how the best fitting RAN model was related to reading and arithmetic outcomes, assessed several months later. Finally in a third step we took a clinical perspective and investigated specific contributions of RAN measures to reading and arithmetic outcomes. While RAN has emerged as a promising predictor of reading, the relationship between RAN and arithmetic has been less examined in the past. Hundred and twenty-two first graders completed seven RAN tasks, each comprising visually familiar stimuli such as digits, vowels, consonants, dice, finger-numeral configurations, objects, and colors. Four months later the same children completed a range of reading and arithmetic tasks. From a general descriptive perspective, structural equation modeling supports a one-dimensional RAN factor in 6- to -7-year-old children. However, from a clinical perspective, our findings emphasize the specific contributions of RANs. Interestingly, alphanumeric RANs (i.e., vowel RAN) were most promising when predicting reading skills and number-specific RANs (i.e., finger-numeral configuration RAN) were most promising when predicting arithmetic fluency. The implications for clinical and educational practices will be discussed.

Real-life C-RAN deployment considerations

DEFF Research Database (Denmark)

Hansen, Line Maria Pyndt; Ruepp, Sarah Renée; Christiansen, Henrik Lehrmann

2017-01-01

procedures and best practices for roll out are yet to be established. This work provides a case study, where a small but densely populated part of the network owned by the Danish mobile network operator, TDC, is evaluated for C-RAN deployment. A roadmap is provided which uses traffic data as input...

Inadequacy representation of flamelet-based RANS model for turbulent non-premixed flame

Science.gov (United States)

Lee, Myoungkyu; Oliver, Todd; Moser, Robert

2017-11-01

Stochastic representations for model inadequacy in RANS-based models of non-premixed jet flames are developed and explored. Flamelet-based RANS models are attractive for engineering applications relative to higher-fidelity methods because of their low computational costs. However, the various assumptions inherent in such models introduce errors that can significantly affect the accuracy of computed quantities of interest. In this work, we develop an approach to represent the model inadequacy of the flamelet-based RANS model. In particular, we pose a physics-based, stochastic PDE for the triple correlation of the mixture fraction. This additional uncertain state variable is then used to construct perturbations of the PDF for the instantaneous mixture fraction, which is used to obtain an uncertain perturbation of the flame temperature. A hydrogen-air non-premixed jet flame is used to demonstrate the representation of the inadequacy of the flamelet-based RANS model. This work was supported by DARPA-EQUiPS(Enabling Quantification of Uncertainty in Physical Systems) program.

Hybrid RANS/LES method for wind flow over complex terrain

DEFF Research Database (Denmark)

Bechmann, Andreas; Sørensen, Niels N.

2010-01-01

for flows at high Reynolds numbers. To reduce the computational cost of traditional LES, a hybrid method is proposed in which the near-wall eddies are modelled in a Reynolds-averaged sense. Close to walls, the flow is treated with the Reynolds-averaged Navier-Stokes (RANS) equations (unsteady RANS...... rough walls. Previous attempts of combining RANS and LES has resulted in unphysical transition regions between the two layers, but the present work improves this region by using a stochastic backscatter model. To demonstrate the ability of the proposed hybrid method, simulations are presented for wind...... the turbulent kinetic energy, whereas the new method captures the high turbulence levels well but underestimates the mean velocity. The presented results are for a relative mild configuration of complex terrain, but the proposed method can also be used for highly complex terrain where the benefits of the new...

Mel-18 interacts with RanGAP1 and inhibits its sumoylation.

Science.gov (United States)

Zhang, Jie; Sarge, Kevin D

2008-10-17

Our previous results showed that the polycomb protein mel-18 binds to a protein called HSF2 and inhibits HSF2 sumoylation, thereby functioning as an anti-SUMO E3 factor. This study also suggested that mel-18 regulates the sumoylation of other cellular proteins, but the identities of these other proteins were unknown. Here we show that mel-18 interacts with the RanGAP1 protein and inhibits its sumoylation, and that these activities do not require the RING domain of mel-18. The results also show that RanGAP1 sumoylation is decreased during mitosis, and that this is associated with increased interaction between RanGAP1 and mel-18 during this stage of the cell cycle. Intriguingly, this regulatory relationship is the opposite of that found for mel-18 and HSF2, in which the interaction between these two proteins decreases during mitosis, resulting in elevated HSF2 sumoylation. The results of this study strengthen the conclusion that mel-18 functions as an anti-SUMO E3 factor, and extend its targets to include regulation of the sumoylation of the important cellular protein RanGAP1.

RANS Simulation of the Separated Flow over a Bump with Active Control

Science.gov (United States)

Iaccarino, Gianluca; Marongiu, Claudio; Catalano, Pietro; Amato, Marcello

2003-01-01

The objective of this paper is to investigate the accuracy of Reynolds-Averaged Navier- Stokes (RANS) techniques in predicting the effect of steady and unsteady flow control devices. This is part of a larger effort in applying numerical simulation tools to investigate of the performance of synthetic jets in high Reynolds number turbulent flows. RANS techniques have been successful in predicting isolated synthetic jets as reported by Kral et al. Nevertheless, due to the complex, and inherently unsteady nature of the interaction between the synthetic jet and the external boundary layer flow, it is not clear whether RANS models can represent the turbulence statistics correctly.

Boundary layers affected by different pressure gradients investigated computationally by a zonal RANS-LES method

International Nuclear Information System (INIS)

Roidl, B.; Meinke, M.; Schröder, W.

2014-01-01

Highlights: • Reformulated synthetic turbulence generation method (RSTGM) is applied. • Zonal RANS-LES method is applied to boundary layers at pressure gradients. • Good agreement with the pure LES and other reference data is obtained. • The RSTGM is applicable to pressure gradient flows without modification. • RANS-to-LES boundary should be located where -1·10 6 6 is satisfied. -- Abstract: The reformulated synthetic turbulence generation (RSTG) method is used to compute by a fully coupled zonal RANS-LES approach turbulent non-zero-pressure gradient boundary layers. The quality of the RSTG method, which is based on the same shape functions and length scale distributions as in zero-pressure gradient flow, is discussed by comparing the zonal RANS-LES findings with pure LES, pure RANS, direct numerical simulation (DNS), and experimental data. For the favorable pressure gradient (FPG) simulation the RANS-to-LES transition occurs in the accelerated flow region and for the adverse pressure gradient (APG) case it is located in the decelerated flow region. The results of the time and spanwise averaged skin-friction distributions, velocity profiles, and Reynolds stress distributions of the zonal RANS-LES simulation show a satisfactory to good agreement with the pure LES, reference DNS, and experimental data. The quality of the findings shows that the rigorous formulation of the synthetic turbulence generation makes the RSTG method applicable without a priori knowledge of the flow properties but those determined by the RANS solution and without using additional control planes to regulate the shear stress budget to a wide range of Reynolds numbers and pressure gradients. The method is a promising approach to formulate embedded RANS-to-LES boundaries in flow regions where the Pohlhausen or acceleration parameter satisfies -1·10 -6 ⩽K⩽2·10 -6

Materials with complex behaviour II properties, non-classical materials and new technologies

CERN Document Server

Oechsner, Andreas

2012-01-01

This book reviews developments and trends in advanced materials and their properties; modeling and simulation of non-classical materials and new technologies for joining materials. Offers tools for characterizing and predicting properties and behavior.

Hybrid RANS/LES applied to complex terrain

DEFF Research Database (Denmark)

Bechmann, Andreas; Sørensen, Niels N.

2011-01-01

Large Eddy Simulation (LES) of the wind in complex terrain is limited by computational cost. The number of computational grid points required to resolve the near-ground turbulent structures (eddies) are very high. The traditional solution to the problem has been to apply a wall function...... aspect ratio in the RANS layer and thereby resolve the mean near-wall velocity profile. The method is applicable to complex terrain and the benefits of traditional LES are kept intact. Using the hybrid method, simulations of the wind over a natural complex terrain near Wellington in New Zealand...... that accounts for the whole near-wall region. Recently, a hybrid method was proposed in which the eddies close to the ground were modelled in a Reynolds-averaged sense (RANS) and the eddies above this region were simulated using LES. The advantage of the approach is the ability to use shallow cells of high...

Noncritical generation of nonclassical frequency combs via spontaneous rotational symmetry breaking

Science.gov (United States)

Navarrete-Benlloch, Carlos; Patera, Giuseppe; de Valcárcel, Germán J.

2017-10-01

Synchronously pumped optical parametric oscillators (SPOPOs) are optical cavities driven by mode-locked lasers, and containing a nonlinear crystal capable of down-converting a frequency comb to lower frequencies. SPOPOs have received a lot of attention lately because their intrinsic multimode nature makes them compact sources of quantum correlated light with promising applications in modern quantum information technologies. In this work we show that SPOPOs are also capable of accessing the challenging and interesting regime where spontaneous symmetry breaking confers strong nonclassical properties to the emitted light, which has eluded experimental observation so far. Apart from opening the possibility of studying experimentally this elusive regime of dissipative phase transitions, our predictions will have a practical impact, since we show that spontaneous symmetry breaking provides a specific spatiotemporal mode with large quadrature squeezing for any value of the system parameters, turning SPOPOs into robust sources of highly nonclassical light above threshold.

Comparison between photon annihilation-then-creation and photon creation-then-annihilation thermal states: Non-classical and non-Gaussian properties

Science.gov (United States)

Xu, Xue-Xiang; Yuan, Hong-Chun; Wang, Yan

2014-07-01

We investigate the nonclassical properties of arbitrary number photon annihilation-then-creation operation (AC) and creation-then-annihilation operation (CA) to the thermal state (TS), whose normalization factors are related to the polylogarithm function. Then we compare their quantum characters, such as photon number distribution, average photon number, Mandel Q-parameter, purity and the Wigner function. Because of the noncommutativity between the annihilation operator and the creation operator, the ACTS and the CATS have different nonclassical properties. It is found that nonclassical properties are exhibited more strongly after AC than after CA. In addition we also examine their non-Gaussianity. The result shows that the ACTS can present a slightly bigger non-Gaussianity than the CATS.

Comparison between photon annihilation-then-creation and photon creation-then-annihilation thermal states: Non-classical and non-Gaussian properties

International Nuclear Information System (INIS)

Xu Xue-Xiang; Wang Yan; Yuan Hong-Chun

2014-01-01

We investigate the nonclassical properties of arbitrary number photon annihilation-then-creation operation (AC) and creation-then-annihilation operation (CA) to the thermal state (TS), whose normalization factors are related to the polylogarithm function. Then we compare their quantum characters, such as photon number distribution, average photon number, Mandel Q-parameter, purity and the Wigner function. Because of the noncommutativity between the annihilation operator and the creation operator, the ACTS and the CATS have different nonclassical properties. It is found that nonclassical properties are exhibited more strongly after AC than after CA. In addition we also examine their non-Gaussianity. The result shows that the ACTS can present a slightly bigger non-Gaussianity than the CATS. (general)

Performance assessment of the RANS turbulence models in nuclear fuel rod bundles

International Nuclear Information System (INIS)

In, Wang Kee; Chun, Tae Hyun; Oh, Dong Seok; Shin, Chang Hwan

2005-02-01

The three experiments for turbulent flow in a rod bundle geometry were simulated in this CFD analysis using various RANS models. The CFD predictions were compared with the experimental and DNS results. The RANS models used here are the nonlinear quadratic/cubic κ-ε models and the second-order closure models (SSG, LRR, RSM-ω). The anisotropic models predicted the secondary flow and showed a significantly improved agreement with the measurements from the standard κ-ε model. In particular, the SSG model resulted in the best performance showing the closest agreement with the experimental results. However, the RANS models could not predict the very high anisotropy observed in a rod bundle with a small pitch-to-diameter ratio

Nonclassicality threshold for the three-qubit Greenberger-Horne-Zeilinger state

Energy Technology Data Exchange (ETDEWEB)

Vertesi, Tamas; Pal, Karoly F. [Institute of Nuclear Research of the Hungarian Academy of Sciences, P.O. Box 51, H-4001 Debrecen (Hungary)

2011-10-15

The nonclassical properties of the noisy three-qubit Greenberger-Horne-Zeilinger (GHZ) states, {rho}{sub v}=v|GHZ>nonclassical for the parameter range 1/2

A nonclassical Radau collocation method for solving the Lane-Emden equations of the polytropic index 4.75 ≤ α < 5

Science.gov (United States)

Tirani, M. D.; Maleki, M.; Kajani, M. T.

2014-11-01

A numerical method for solving the Lane-Emden equations of the polytropic index α when 4.75 ≤ α ≤ 5 is introduced. The method is based upon nonclassical Gauss-Radau collocation points and Freud type weights. Nonclassical orthogonal polynomials, nonclassical Radau points and weighted interpolation are introduced and are utilized in the interval [0,1]. A smooth, strictly monotonic transformation is used to map the infinite domain x ∈ [0,∞) onto a half-open interval t ∈ [0,1). The resulting problem on the finite interval is then transcribed to a system of nonlinear algebraic equations using collocation. The method is easy to implement and yields very accurate results.

Reproducibility of Psychological Experiments as a Problem of Post-Nonclassical Science

Directory of Open Access Journals (Sweden)

Vachkov I.V.,

2016-04-01

Full Text Available A fundamental project on reproducibility carried out in the USA by Brian Nosek in 2015 (the Reproducibility Project revealed a serious methodological problem in psychology: the issue of replication of psycho- logical experiments. Reproducibility has been traditionally perceived as one of the basic principles of the scientific method. However, methodological analysis of the modern post-nonclassical stage in the development of science suggests that this might be a bit too uncompromising as applied to psychology. It seems that the very criteria of scientific research need to be reconsidered with regard to the specifics of post-nonclassical science, and, as the authors put it, as a result, reproducibility might lose its key status or even be excluded at all. The reviewed problem and the proposed ways of coping with it are of high importance to research and practice in psychology as they define the strategies for organizing, conducting and evaluating experimental research.

Nonclassical Effects of a Four-Level Excited-Doublet Atom Model

International Nuclear Information System (INIS)

Zhang Jiansong; Xu Jingbo

2006-01-01

We adopt a dynamical algebraic method to study a four-level excited-doublet atom model and obtain the explicit expressions of the time-evolution operator and the density operator for the system. The nonclassical effects of the system, such as collapses and revivals of the atomic inversion and squeezing of the radiation field, are also discussed.

Ran GTPase-activating protein 1 is a therapeutic target in diffuse large B-cell lymphoma.

Directory of Open Access Journals (Sweden)

Kung-Chao Chang

Full Text Available Lymphoma-specific biomarkers contribute to therapeutic strategies and the study of tumorigenesis. Diffuse large B-cell lymphoma (DLBCL is the most common type of malignant lymphoma. However, only 50% of patients experience long-term survival after current treatment; therefore, developing novel therapeutic strategies is warranted. Comparative proteomic analysis of two DLBCL lines with a B-lymphoblastoid cell line (LCL showed differential expression of Ran GTPase-activating protein 1 (RanGAP1 between them, which was confirmed using immunoblotting. Immunostaining showed that the majority of DLBCLs (92%, 46/50 were RanGAP1(+, while reactive lymphoid hyperplasia (n = 12 was RanGAP1(+ predominantly in germinal centers. RanGAP1 was also highly expressed in other B-cell lymphomas (BCL, n = 180 with brisk mitotic activity (B-lymphoblastic lymphoma/leukemia: 93%, and Burkitt lymphoma: 95% or cell-cycle dysregulation (mantle cell lymphoma: 83%, and Hodgkin's lymphoma 91%. Interestingly, serum RanGAP1 level was higher in patients with high-grade BCL (1.71 ± 2.28 ng/mL, n = 62 than in low-grade BCL (0.75 ± 2.12 ng/mL, n = 52 and healthy controls (0.55 ± 1.58 ng/mL, n = 75 (high-grade BCL vs. low-grade BCL, p = 0.002; high-grade BCL vs. control, p < 0.001, Mann-Whitney U test. In vitro, RNA interference of RanGAP1 showed no effect on LCL but enhanced DLBCL cell death (41% vs. 60%; p = 0.035 and cell-cycle arrest (G0/G1: 39% vs. 49%, G2/M: 19.0% vs. 7.5%; p = 0.030 along with decreased expression of TPX2 and Aurora kinases, the central regulators of mitotic cell division. Furthermore, ON 01910.Na (Estybon, a multikinase inhibitor induced cell death, mitotic cell arrest, and hyperphosphorylation of RanGAP1 in DLBCL cell lines but no effects in normal B and T cells. Therefore, RanGAP1 is a promising marker and therapeutic target for aggressive B-cell lymphoma, especially DLBCL.

Nonlinear coherent loss for generating non-classical states

International Nuclear Information System (INIS)

Mikhalychev, A; Mogilevtsev, D; Kilin, S

2011-01-01

Here, we discuss a generation of non-classical states of bosonic mode with the help of artificially designed loss, namely the nonlinear coherent loss. We show how to generate superpositions of Fock states, and how it is possible to 'comb' the initial states leaving only states with certain properties in the resulting superposition (for example, a generation of a superposition of Fock states with odd number of particles). We discuss purity of generated states and estimate maximal achievable generation fidelity.

Time-dependent LXR/RXR pathway modulation characterizes capillary remodeling in inflammatory corneal neovascularization.

Science.gov (United States)

Mukwaya, Anthony; Lennikov, Anton; Xeroudaki, Maria; Mirabelli, Pierfrancesco; Lachota, Mieszko; Jensen, Lasse; Peebo, Beatrice; Lagali, Neil

2018-05-01

Inflammation in the normally immune-privileged cornea can initiate a pathologic angiogenic response causing vision-threatening corneal neovascularization. Inflammatory pathways, however, are numerous, complex and are activated in a time-dependent manner. Effective resolution of inflammation and associated angiogenesis in the cornea requires knowledge of these pathways and their time dependence, which has, to date, remained largely unexplored. Here, using a model of endogenous resolution of inflammation-induced corneal angiogenesis, we investigate the time dependence of inflammatory genes in effecting capillary regression and the return of corneal transparency. Endogenous capillary regression was characterized by a progressive thinning and remodeling of angiogenic capillaries and inflammatory cell retreat in vivo in the rat cornea. By whole-genome longitudinal microarray analysis, early suppression of VEGF ligand-receptor signaling and inflammatory pathways preceded an unexpected later-phase preferential activation of LXR/RXR, PPARα/RXRα and STAT3 canonical pathways, with a concurrent attenuation of LPS/IL-1 inhibition of RXR function and Wnt/β-catenin signaling pathways. Potent downstream inflammatory cytokines such as Cxcl5, IL-1β, IL-6 and Ccl2 were concomitantly downregulated during the remodeling phase. Upstream regulators of the inflammatory pathways included Socs3, Sparc and ApoE. A complex and coordinated time-dependent interplay between pro- and anti-inflammatory signaling pathways highlights a potential anti-inflammatory role of LXR/RXR, PPARα/RXRα and STAT3 signaling pathways in resolving inflammatory corneal angiogenesis.

Nonclassical light sources for silicon photonics

Science.gov (United States)

Bajoni, Daniele; Galli, Matteo

2017-09-01

Quantum photonics has recently attracted a lot of attention for its disruptive potential in emerging technologies like quantum cryptography, quantum communication and quantum computing. Driven by the impressive development in nanofabrication technologies and nanoscale engineering, silicon photonics has rapidly become the platform of choice for on-chip integration of high performing photonic devices, now extending their functionalities towards quantum-based applications. Focusing on quantum Information Technology (qIT) as a key application area, we review recent progress in integrated silicon-based sources of nonclassical states of light. We assess the state of the art in this growing field and highlight the challenges that need to be overcome to make quantum photonics a reliable and widespread technology.

Nuclear translocation of glutathione S-transferase {pi} is mediated by a non-classical localization signal

Energy Technology Data Exchange (ETDEWEB)

Kawakatsu, Miho [Department of Stem Cell Biology, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8523 (Japan); Goto, Shinji, E-mail: sgoto@nagasaki-u.ac.jp [Department of Stem Cell Biology, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8523 (Japan); Yoshida, Takako; Urata, Yoshishige; Li, Tao-Sheng [Department of Stem Cell Biology, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8523 (Japan)

2011-08-12

Highlights: {yields} Nuclear translocation of GST{pi} is abrogated by the deletion of the last 16 amino acid residues in the carboxy-terminal region, indicating that residues 195-208 of GST{pi} are required for nuclear translocation. {yields} The lack of a contiguous stretch of positively charged amino acid residues within the carboxy-terminal region of GST{pi}, suggests that the nuclear translocation of GST{pi} is mediated by a non-classical nuclear localization signal. {yields} An in vitro transport assay shows that the nuclear translocation of GST{pi} is dependent on cytosolic factors and ATP. -- Abstract: Glutathione S-transferase {pi} (GST{pi}), a member of the GST family of multifunctional enzymes, is highly expressed in human placenta and involved in the protection of cellular components against electrophilic compounds or oxidative stress. We have recently found that GST{pi} is expressed in the cytoplasm, mitochondria, and nucleus in some cancer cells, and that the nuclear expression of GST{pi} appears to correlate with resistance to anti-cancer drugs. Although the mitochondrial targeting signal of GST{pi} was previously identified in the amino-terminal region, the mechanism of nuclear translocation remains completely unknown. In this study, we find that the region of GST{pi}195-208 is critical for nuclear translocation, which is mediated by a novel and non-classical nuclear localization signal. In addition, using an in vitro transport assay, we demonstrate that the nuclear translocation of GST{pi} depends on the cytosolic extract and ATP. Although further experiments are needed to understand in depth the precise mechanism of nuclear translocation of GST{pi}, our results may help to establish more efficient anti-cancer therapy, especially with respect to resistance to anti-cancer drugs.

Unconventional secretion of tissue transglutaminase involves phospholipid-dependent delivery into recycling endosomes.

Directory of Open Access Journals (Sweden)

Evgeny A Zemskov

2011-04-01

Full Text Available Although endosomal compartments have been suggested to play a role in unconventional protein secretion, there is scarce experimental evidence for such involvement. Here we report that recycling endosomes are essential for externalization of cytoplasmic secretory protein tissue transglutaminase (tTG. The de novo synthesized cytoplasmic tTG does not follow the classical ER/Golgi-dependent secretion pathway, but is targeted to perinuclear recycling endosomes, and is delivered inside these vesicles prior to externalization. On its route to the cell surface tTG interacts with internalized β1 integrins inside the recycling endosomes and is secreted as a complex with recycled β1 integrins. Inactivation of recycling endosomes, blocking endosome fusion with the plasma membrane, or downregulation of Rab11 GTPase that controls outbound trafficking of perinuclear recycling endosomes, all abrogate tTG secretion. The initial recruitment of cytoplasmic tTG to recycling endosomes and subsequent externalization depend on its binding to phosphoinositides on endosomal membranes. These findings begin to unravel the unconventional mechanism of tTG secretion which utilizes the long loop of endosomal recycling pathway and indicate involvement of endosomal trafficking in non-classical protein secretion.

General and Specific Contributions of RAN to Reading and Arithmetic Fluency in First Graders: A Longitudinal Latent Variable Approach

OpenAIRE

Caroline Hornung; Romain Martin; Michel Fayol; Michel Fayol

2017-01-01

In the present study, we opted for a longitudinal design and examined rapid automatized naming (RAN) performance from two perspectives. In a first step, we examined the structure of RAN performance from a general cognitive perspective. We investigated whether rapid naming measures (e.g., digit RAN and color RAN) reflect a mainly domain-general factor or domain-specific factors. In a second step, we examined how the best fitting RAN model was related to reading and arithmetic outcomes, assesse...

Non-classical homogeneous precipitation mediated by compositional fluctuations in titanium alloys

International Nuclear Information System (INIS)

Nag, S.; Zheng, Y.; Williams, R.E.A.; Devaraj, A.; Boyne, A.; Wang, Y.; Collins, P.C.; Viswanathan, G.B.; Tiley, J.S.; Muddle, B.C.; Banerjee, R.

2012-01-01

This paper presents experimental evidence of homogeneous precipitation of the α-phase within the β matrix of a titanium alloy, and then accounts for this phase transformation by a new, non-classical mechanism involving compositional fluctuations, based on the pseudo-spinodal concept [1]. This mechanism involves local compositional fluctuations of small amplitude which, when of a certain magnitude, can favor thermodynamically certain regions of the β matrix to transform congruently to the α-phase but with compositions far from equilibrium. Subsequently, as measured experimentally using the tomographical atom probe, continuous diffusional partitioning between the parent β- and product α-phases during isothermal annealing drives their compositions towards equilibrium. For a given alloy composition, the decomposition mechanism is strongly temperature dependent, which would be expected for homogeneous precipitation via the compositional fluctuation-mediated mechanism but not necessarily for one based on classical nucleation theory. The applicability of this mechanism to phase transformations in general is noted.

Higher-order sub-Poissonian-like nonclassical fields: Theoretical and experimental comparison

Czech Academy of Sciences Publication Activity Database

Peřina Jr., J.; Michálek, Václav; Haderka, O.

2017-01-01

Roč. 96, č. 3 (2017), s. 1-7, č. článku 033852. ISSN 2469-9926 Institutional support: RVO:68378271 Keywords : twin beams * photon statistics * sub-Poissonian-like nonclassical fields Subject RIV: BH - Optics, Masers, Lasers OBOR OECD: Optics (including laser optics and quantum optics) Impact factor: 2.925, year: 2016

Developmental pathways from child maltreatment to adolescent marijuana dependence: Examining moderation by FKBP5

Science.gov (United States)

Handley, Elizabeth D.; Rogosch, Fred A.; Cicchetti, Dante

2015-01-01

The current study examined the prospective association between child maltreatment and the development of substance use disorder (SUD) in adolescence with the aim of investigating pathways underlying this relation, as well as genetic moderation of these developmental mechanisms. Specifically, we tested whether youth who experienced maltreatment prior to age 8 were at risk for the development of marijuana dependence in adolescence by way of a childhood externalizing pathway and a childhood internalizing pathway. Moreover, we tested whether variation in FKBP5 CATT haplotype moderated these pathways. The participants were 326 children (n=179 maltreated; n=147 nonmaltreated) assessed across two waves of data collection (childhood: ages 7–9 and adolescence: ages 15–18). Results indicated that higher levels of child externalizing symptoms significantly mediated the effect of child maltreatment on adolescent marijuana dependence symptoms for individuals with 1–2 copies of the FKBP5 CATT haplotype only. We did not find support for an internalizing pathway from child maltreatment to adolescent marijuana dependence, nor did we find evidence of moderation of the internalizing pathway by FKBP5 haplotype variation. Findings extend previous research by demonstrating that whether a maltreated child will traverse an externalizing pathway toward SUD in adolescence is dependent on FKBP5 genetic variation. PMID:26535939

An Enhanced OFDM Resource Allocation Algorithm in C-RAN Based 5G Public Safety Network

Directory of Open Access Journals (Sweden)

Lei Feng

2016-01-01

Full Text Available Public Safety Network (PSN is the network for critical communication when disaster occurs. As a key technology in 5G, Cloud-Radio Access Network (C-RAN can play an important role in PSN instead of LTE-based RAN. This paper firstly introduces C-RAN based PSN architecture and models the OFDM resource allocation problem in C-RAN based PSN as an integer quadratic programming, which allows the trade-off between expected bitrates and allocating fairness of PSN Service User (PSU. However, C-RAN based PSN needs to improve the efficiency of allocating algorithm because of a mass of PSU-RRH associations when disaster occurs. To deal with it, the resources allocating problem with integer variables is relaxed into one with continuous variables in the first step and an algorithm based on Generalized Bender’s Decomposition (GBD is proposed to solve it. Then we use Feasible Pump (FP method to get a feasible integer solution on the original OFDM resources allocation problem. The final experiments show the total throughput achieved by C-RAN based PSN is at most higher by 19.17% than the LTE-based one. And the average computational time of the proposed GBD and FP algorithm is at most lower than Barrier by 51.5% and GBD with no relaxation by 30.1%, respectively.

Assessment of Reynolds stresses tensor reconstruction methods for synthetic turbulent inflow conditions. Application to hybrid RANS/LES methods

International Nuclear Information System (INIS)

Laraufie, Romain; Deck, Sébastien

2013-01-01

Highlights: • Present various Reynolds stresses reconstruction methods from a RANS-SA flow field. • Quantify the accuracy of the reconstruction methods for a wide range of Reynolds. • Evaluate the capabilities of the overall process (Reconstruction + SEM). • Provide practical guidelines to realize a streamwise RANS/LES (or WMLES) transition. -- Abstract: Hybrid or zonal RANS/LES approaches are recognized as the most promising way to accurately simulate complex unsteady flows under current computational limitations. One still open issue concerns the transition from a RANS to a LES or WMLES resolution in the stream-wise direction, when near wall turbulence is involved. Turbulence content has then to be prescribed at the transition to prevent from turbulence decay leading to possible flow relaminarization. The present paper aims to propose an efficient way to generate this switch, within the flow, based on a synthetic turbulence inflow condition, named Synthetic Eddy Method (SEM). As the knowledge of the whole Reynolds stresses is often missing, the scope of this paper is focused on generating the quantities required at the SEM inlet from a RANS calculation, namely the first and second order statistics of the aerodynamic field. Three different methods based on two different approaches are presented and their capability to accurately generate the needed aerodynamic values is investigated. Then, the ability of the combination SEM + Reconstruction method to manufacture well-behaved turbulence is demonstrated through spatially developing flat plate turbulent boundary layers. In the mean time, important intrinsic features of the Synthetic Eddy method are pointed out. The necessity of introducing, within the SEM, accurate data, with regards to the outer part of the boundary layer, is illustrated. Finally, user’s guidelines are given depending on the Reynolds number based on the momentum thickness, since one method is suitable for low Reynolds number while the

Nonclassical photon streams using rephased amplified spontaneous emission

International Nuclear Information System (INIS)

Ledingham, Patrick M.; Naylor, William R.; Longdell, Jevon J.; Beavan, Sarah E.; Sellars, Matthew J.

2010-01-01

We present a fully quantum mechanical treatment of optically rephased photon echoes. These echoes exhibit noise due to amplified spontaneous emission; however, this noise can be seen as a consequence of the entanglement between the atoms and the output light. With a rephasing pulse one can get an 'echo' of the amplified spontaneous emission, leading to light with nonclassical correlations at points separated in time, which is of interest in the context of building wide bandwith quantum repeaters. We also suggest a wideband version of DLCZ protocol based on the same ideas.

A non-classical view of the modulation of mineral precipitation by organic additives

Science.gov (United States)

Ruiz-Agudo, Encarnacion; Ruiz-Agudo, Cristina; Burgos-Cara, Alejandro; Putnis, Christine; Rodriguez-Navarro, Carlos; Putnis, Andrew

2016-04-01

Questions persist on the mechanisms of crystallization of sparingly soluble minerals such as calcium carbonate, calcium oxalate or barium sulphate. Compared to CaCO3, the mechanisms of nucleation and growth in the CaC2O4-H2O or BaSO4-H2O systems have received less attention. These phases are important due to their relevance as biominerals and/or unwanted mineral deposits in technological applications. Growing evidence suggests that sparingly soluble salts form by non-classical nucleation and growth pathways, where pre-nucleation ion associates and amorphous (solid or liquid) precursor phase(s) play a critical role (e.g. Rodríguez-Navarro et al. (2015), Ruiz-Agudo et al. (2015)). Indeed the identification of pre-nucleation species in these systems and their strong interactions with organic compounds (Verch et al. 2011) raises the possibility that the control of organics on biomineralization may begin even earlier than previously thought. A sound knowledge of the physical mechanisms by which acidic macromolecules affect nucleation and early growth may offer general insights concerning the molecular control of biomineralization, as well as being critical for improving strategies to control unwanted mineral deposition or for the synthesis of biomimetic materials. Here we present investigations on the initial stages of the precipitation of these relevant minerals in organic-free solutions to identify the precipitation pathway and to look for any potential precursor phase(s) to the final, crystalline polymorph. As well, we explore the effects that several acidic organic compounds have on the different precipitation stages identified. We find that organic additives such as citric acid, polyacrilic acid or a commercial copolymer of maleic acid/allyl sulfonic acid with phosphonate groups can be active at modifying pre-nucleation stages (destabilizing of pre-nucleation species or hampering the aggregation and growth of pre-nucleation associates) and subsequently strongly

[A non-classical approach to medical practices: Michel Foucault and Actor-Network Theory].

Science.gov (United States)

Bińczyk, E

2001-01-01

The text presents an analysis of medical practices stemming from two sources: Michel Foucault's conception and the research of Annemarie Mol and John Law, representatives of a trend known as Actor-Network Theory. Both approaches reveal significant theoretical kinship: they can be successfully consigned to the framework of non-classical sociology of science. I initially refer to the cited conceptions as a version of non-classical sociology of medicine. The identity of non-classical sociology of medicine hinges on the fact that it undermines the possibility of objective definitions of disease, health and body. These are rather approached as variable social and historical phenomena, co-constituted by medical practices. To both Foucault and Mol the main object of interest was not medicine as such, but rather the network of medical practices. Mol and Law sketch a new theoretical perspective for the analysis of medical practices. They attempt to go beyond the dichotomous scheme of thinking about the human body as an object of medical research and the subject of private experience. Research on patients suffering blood-sugar deficiency provide the empirical background for the thesis of Actor-Network Theory representatives. Michel Foucault's conceptions are extremely critical of medical practices. The French researcher describes the processes of 'medicalising' Western society as the emergence of a new type of power. He attempts to sensitise the reader to the ethical dimension of the processes of medicalising society.

Arctigenin inhibits osteoclast differentiation and function by suppressing both calcineurin-dependent and osteoblastic cell-dependent NFATc1 pathways.

Science.gov (United States)

Yamashita, Teruhito; Uehara, Shunsuke; Udagawa, Nobuyuki; Li, Feng; Kadota, Shigetoshi; Esumi, Hiroyasu; Kobayashi, Yasuhiro; Takahashi, Naoyuki

2014-01-01

Arctigenin, a lignan-derived compound, is a constituent of the seeds of Arctium lappa. Arctigenin was previously shown to inhibit osteoclastogenesis; however, this inhibitory mechanism has yet to be elucidated. Here, we showed that arctigenin inhibited the action of nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1), a key transcription factor for osteoclastogenesis. NFATc1 in osteoclast precursors was activated through two distinct pathways: the calcineurin-dependent and osteoblastic cell-dependent pathways. Among the several lignan-derived compounds examined, arctigenin most strongly inhibited receptor activator of nuclear factor κB ligand (RANKL)-induced osteoclast-like cell formation in mouse bone marrow macrophage (BMM) cultures, in which the calcineurin-dependent NFATc1 pathway was activated. Arctigenin suppressed neither the activation of nuclear factor κB and mitogen-activated protein kinases nor the up-regulation of c-Fos expression in BMMs treated with RANKL. However, arctigenin suppressed RANKL-induced NFATc1 expression. Interestingly, the treatment of osteoclast-like cells with arctigenin converted NFATc1 into a lower molecular weight species, which was translocated into the nucleus even in the absence of RANKL. Nevertheless, arctigenin as well as cyclosporin A (CsA), a calcineurin inhibitor, suppressed the NFAT-luciferase reporter activity induced by ionomycin and phorbol 12-myristate 13-acetate in BMMs. Chromatin immunoprecipitation analysis confirmed that arctigenin inhibited the recruitment of NFATc1 to the promoter region of the NFATc1 target gene. Arctigenin, but not CsA suppressed osteoclast-like cell formation in co-cultures of osteoblastic cells and bone marrow cells, in which the osteoblastic cell-dependent NFATc1 pathway was activated. The forced expression of constitutively active NFATc1 rescued osteoclastogenesis in BMM cultures treated with CsA, but not that treated with arctigenin. Arctigenin also suppressed the pit

Arctigenin Inhibits Osteoclast Differentiation and Function by Suppressing Both Calcineurin-Dependent and Osteoblastic Cell-Dependent NFATc1 Pathways

Science.gov (United States)

Yamashita, Teruhito; Uehara, Shunsuke; Udagawa, Nobuyuki; Li, Feng; Kadota, Shigetoshi; Esumi, Hiroyasu; Kobayashi, Yasuhiro; Takahashi, Naoyuki

2014-01-01

Arctigenin, a lignan-derived compound, is a constituent of the seeds of Arctium lappa. Arctigenin was previously shown to inhibit osteoclastogenesis; however, this inhibitory mechanism has yet to be elucidated. Here, we showed that arctigenin inhibited the action of nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1), a key transcription factor for osteoclastogenesis. NFATc1 in osteoclast precursors was activated through two distinct pathways: the calcineurin-dependent and osteoblastic cell-dependent pathways. Among the several lignan-derived compounds examined, arctigenin most strongly inhibited receptor activator of nuclear factor κB ligand (RANKL)-induced osteoclast-like cell formation in mouse bone marrow macrophage (BMM) cultures, in which the calcineurin-dependent NFATc1 pathway was activated. Arctigenin suppressed neither the activation of nuclear factor κB and mitogen-activated protein kinases nor the up-regulation of c-Fos expression in BMMs treated with RANKL. However, arctigenin suppressed RANKL-induced NFATc1 expression. Interestingly, the treatment of osteoclast-like cells with arctigenin converted NFATc1 into a lower molecular weight species, which was translocated into the nucleus even in the absence of RANKL. Nevertheless, arctigenin as well as cyclosporin A (CsA), a calcineurin inhibitor, suppressed the NFAT-luciferase reporter activity induced by ionomycin and phorbol 12-myristate 13-acetate in BMMs. Chromatin immunoprecipitation analysis confirmed that arctigenin inhibited the recruitment of NFATc1 to the promoter region of the NFATc1 target gene. Arctigenin, but not CsA suppressed osteoclast-like cell formation in co-cultures of osteoblastic cells and bone marrow cells, in which the osteoblastic cell-dependent NFATc1 pathway was activated. The forced expression of constitutively active NFATc1 rescued osteoclastogenesis in BMM cultures treated with CsA, but not that treated with arctigenin. Arctigenin also suppressed the pit

Arctigenin inhibits osteoclast differentiation and function by suppressing both calcineurin-dependent and osteoblastic cell-dependent NFATc1 pathways.

Directory of Open Access Journals (Sweden)

Teruhito Yamashita

Full Text Available Arctigenin, a lignan-derived compound, is a constituent of the seeds of Arctium lappa. Arctigenin was previously shown to inhibit osteoclastogenesis; however, this inhibitory mechanism has yet to be elucidated. Here, we showed that arctigenin inhibited the action of nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1, a key transcription factor for osteoclastogenesis. NFATc1 in osteoclast precursors was activated through two distinct pathways: the calcineurin-dependent and osteoblastic cell-dependent pathways. Among the several lignan-derived compounds examined, arctigenin most strongly inhibited receptor activator of nuclear factor κB ligand (RANKL-induced osteoclast-like cell formation in mouse bone marrow macrophage (BMM cultures, in which the calcineurin-dependent NFATc1 pathway was activated. Arctigenin suppressed neither the activation of nuclear factor κB and mitogen-activated protein kinases nor the up-regulation of c-Fos expression in BMMs treated with RANKL. However, arctigenin suppressed RANKL-induced NFATc1 expression. Interestingly, the treatment of osteoclast-like cells with arctigenin converted NFATc1 into a lower molecular weight species, which was translocated into the nucleus even in the absence of RANKL. Nevertheless, arctigenin as well as cyclosporin A (CsA, a calcineurin inhibitor, suppressed the NFAT-luciferase reporter activity induced by ionomycin and phorbol 12-myristate 13-acetate in BMMs. Chromatin immunoprecipitation analysis confirmed that arctigenin inhibited the recruitment of NFATc1 to the promoter region of the NFATc1 target gene. Arctigenin, but not CsA suppressed osteoclast-like cell formation in co-cultures of osteoblastic cells and bone marrow cells, in which the osteoblastic cell-dependent NFATc1 pathway was activated. The forced expression of constitutively active NFATc1 rescued osteoclastogenesis in BMM cultures treated with CsA, but not that treated with arctigenin. Arctigenin also suppressed the

A gene expression signature of RAS pathway dependence predicts response to PI3K and RAS pathway inhibitors and expands the population of RAS pathway activated tumors.

Science.gov (United States)

Loboda, Andrey; Nebozhyn, Michael; Klinghoffer, Rich; Frazier, Jason; Chastain, Michael; Arthur, William; Roberts, Brian; Zhang, Theresa; Chenard, Melissa; Haines, Brian; Andersen, Jannik; Nagashima, Kumiko; Paweletz, Cloud; Lynch, Bethany; Feldman, Igor; Dai, Hongyue; Huang, Pearl; Watters, James

2010-06-30

Hyperactivation of the Ras signaling pathway is a driver of many cancers, and RAS pathway activation can predict response to targeted therapies. Therefore, optimal methods for measuring Ras pathway activation are critical. The main focus of our work was to develop a gene expression signature that is predictive of RAS pathway dependence. We used the coherent expression of RAS pathway-related genes across multiple datasets to derive a RAS pathway gene expression signature and generate RAS pathway activation scores in pre-clinical cancer models and human tumors. We then related this signature to KRAS mutation status and drug response data in pre-clinical and clinical datasets. The RAS signature score is predictive of KRAS mutation status in lung tumors and cell lines with high (> 90%) sensitivity but relatively low (50%) specificity due to samples that have apparent RAS pathway activation in the absence of a KRAS mutation. In lung and breast cancer cell line panels, the RAS pathway signature score correlates with pMEK and pERK expression, and predicts resistance to AKT inhibition and sensitivity to MEK inhibition within both KRAS mutant and KRAS wild-type groups. The RAS pathway signature is upregulated in breast cancer cell lines that have acquired resistance to AKT inhibition, and is downregulated by inhibition of MEK. In lung cancer cell lines knockdown of KRAS using siRNA demonstrates that the RAS pathway signature is a better measure of dependence on RAS compared to KRAS mutation status. In human tumors, the RAS pathway signature is elevated in ER negative breast tumors and lung adenocarcinomas, and predicts resistance to cetuximab in metastatic colorectal cancer. These data demonstrate that the RAS pathway signature is superior to KRAS mutation status for the prediction of dependence on RAS signaling, can predict response to PI3K and RAS pathway inhibitors, and is likely to have the most clinical utility in lung and breast tumors.

A gene expression signature of RAS pathway dependence predicts response to PI3K and RAS pathway inhibitors and expands the population of RAS pathway activated tumors

Directory of Open Access Journals (Sweden)

Paweletz Cloud

2010-06-01

Full Text Available Abstract Background Hyperactivation of the Ras signaling pathway is a driver of many cancers, and RAS pathway activation can predict response to targeted therapies. Therefore, optimal methods for measuring Ras pathway activation are critical. The main focus of our work was to develop a gene expression signature that is predictive of RAS pathway dependence. Methods We used the coherent expression of RAS pathway-related genes across multiple datasets to derive a RAS pathway gene expression signature and generate RAS pathway activation scores in pre-clinical cancer models and human tumors. We then related this signature to KRAS mutation status and drug response data in pre-clinical and clinical datasets. Results The RAS signature score is predictive of KRAS mutation status in lung tumors and cell lines with high (> 90% sensitivity but relatively low (50% specificity due to samples that have apparent RAS pathway activation in the absence of a KRAS mutation. In lung and breast cancer cell line panels, the RAS pathway signature score correlates with pMEK and pERK expression, and predicts resistance to AKT inhibition and sensitivity to MEK inhibition within both KRAS mutant and KRAS wild-type groups. The RAS pathway signature is upregulated in breast cancer cell lines that have acquired resistance to AKT inhibition, and is downregulated by inhibition of MEK. In lung cancer cell lines knockdown of KRAS using siRNA demonstrates that the RAS pathway signature is a better measure of dependence on RAS compared to KRAS mutation status. In human tumors, the RAS pathway signature is elevated in ER negative breast tumors and lung adenocarcinomas, and predicts resistance to cetuximab in metastatic colorectal cancer. Conclusions These data demonstrate that the RAS pathway signature is superior to KRAS mutation status for the prediction of dependence on RAS signaling, can predict response to PI3K and RAS pathway inhibitors, and is likely to have the most clinical

RANS / LES coupling applied to high Reynolds number turbulent flows of the nuclear industry; Application du couplage RANS / LES aux ecoulements turbulents a haut nombre de Reynolds de l'industrie nucleaire

Energy Technology Data Exchange (ETDEWEB)

Benarafa, Y

2005-12-15

The main issue to perform a computational study of high Reynolds numbered turbulent flows consists on predicting their unsteadiness without implying a tremendous computational cost. First, the main drawbacks of large-eddy simulation with standard wall model on a coarse mesh for a plane channel flow are highlighted. To correct these drawbacks two coupling RANS/LES methods have been proposed. The first one relies on a sophisticated wall model (TBLE) which consists on solving Thin Boundary Layer Equations with a RANS type turbulent closure in the near wall region. The second one consists on a RANS/LES methods have been proposed. The second one consists on a RANS/LES coupling method using a forcing term approach. These various approaches have been implemented in the TRIO-U code developed at CEA (French Atomic Center) at Grenoble, France. The studied flow configurations are the fully developed plane channel flow and a flow around a surface-mounted cubical obstacle. Both approaches provide encouraging results and allow a surface-mounted cubical obstacle. Both approaches provide encouraging results and allow unsteady simulations for a low computational cost. (author)

Does ability to establish sound-symbol pairings mediate the RAN reading relationship?

DEFF Research Database (Denmark)

Poulsen, Mads; Juul, Holger; Elbro, Carsten

for animals in a paired associate learning task. These animals were then used in a rapid naming task. Results Preliminary results show that reading correlated with the amount of training required for learning the animal names (r=-.19, p=.06). RAN speed with the same animals did not correlate with reading......Performance on tests to rapidly name letters and digits has been shown to correlate with reading. One possible reason is that these tests probe the ability to learn and automatise symbol-sound associations. However, most studies have not controlled for the amount of experience with the RAN......-items, so it is unclear whether it is the experience or the ability to take advantage of the experience that is responsible for the correlation between RAN and reading. Paired associate learning tasks have been shown to differentiate dyslexics from controls, and to correlate with reading in unselected...

Ran GTPase protein promotes human pancreatic cancer proliferation by deregulating the expression of Survivin and cell cycle proteins

International Nuclear Information System (INIS)

Deng, Lin; Lu, Yuanyuan; Zhao, Xiaodi; Sun, Yi; Shi, Yongquan; Fan, Hongwei; Liu, Changhao; Zhou, Jinfeng; Nie, Yongzhan; Wu, Kaichun; Fan, Daiming; Guo, Xuegang

2013-01-01

Highlights: •Overexpression of Ran in pancreatic cancer was correlated with histological grade. •Downregulation of Ran could induce cell apoptosis and inhibit cell proliferation. •The effects were mediated by cell cycle proteins, Survivin and cleaved Caspase-3. -- Abstract: Ran, a member of the Ras GTPase family, has important roles in nucleocytoplasmic transport. Herein, we detected Ran expression in pancreatic cancer and explored its potential role on tumour progression. Overexpressed Ran in pancreatic cancer tissues was found highly correlated with the histological grade. Downregulation of Ran led to significant suppression of cell proliferation, cell cycle arrest at the G1/S phase and induction of apoptosis. In vivo studies also validated that result. Further studies revealed that those effects were at least partly mediated by the downregulation of Cyclin A, Cyclin D1, Cyclin E, CDK2, CDK4, phospho-Rb and Survivin proteins and up regulation of cleaved Caspase-3

Non-classical Correlations and Quantum Coherence in Mixed Environments

Science.gov (United States)

Hu, Zheng-Da; Wei, Mei-Song; Wang, Jicheng; Zhang, Yixin; He, Qi-Liang

2018-05-01

We investigate non-classical correlations (entanglement and quantum discord) and quantum coherence for an open two-qubit system each independently coupled to a bosonic environment and a spin environment, respectively. The modulating effects of spin environment and bosonic environment are respectively explored. A relation among the quantum coherence, quantum discord and classical correlation is found during the sudden transition phenomenon. We also compare the case of mixed environments with that of the same environments, showing that the dynamics is dramatically changed.

On the use of (U)RANS and LES approaches for turbulent incompressible single phase flows in nuclear engineering applications

Energy Technology Data Exchange (ETDEWEB)

Benhamadouche, Sofiane, E-mail: sofiane.benhamadouche@edf.fr

2017-02-15

Highlights: • The paper deals with the use of (U)RANS and LES in nuclear engineering applications. • It gives some ideas and guidelines to run high quality computations. • Some perspectives are drawn concerning the development of (U)RANS and LES approaches in the future. - Abstract: The present paper gives some ideas and guidelines in order to run high quality (U)RANS or LES computations. The paper starts with (U)RANS approaches, advocating the use of Reynolds Stress Models for complex flows and recommending further work on modeling of turbulent heat fluxes, which remains today too basic in industry. The superiority of wall-resolved models vs. wall-modeled in RANS is recalled and the use of adaptive wall treatment is suggested. The concept of Unsteady RANS is finally questioned. Then, important issues around LES are raised. The mesh refinement criteria are recalled for wall-resolved LES and the use of wall models addressed. The production of DNS and wall-resolved LES calculations for flow understanding and RANS validation is encouraged.

Data-free and data-driven spectral perturbations for RANS UQ

Science.gov (United States)

Edeling, Wouter; Mishra, Aashwin; Iaccarino, Gianluca

2017-11-01

Despite recent developments in high-fidelity turbulent flow simulations, RANS modeling is still vastly used by industry, due to its inherent low cost. Since accuracy is a concern in RANS modeling, model-form UQ is an essential tool for assessing the impacts of this uncertainty on quantities of interest. Applying the spectral decomposition to the modeled Reynolds-Stress Tensor (RST) allows for the introduction of decoupled perturbations into the baseline intensity (kinetic energy), shape (eigenvalues), and orientation (eigenvectors). This constitutes a natural methodology to evaluate the model form uncertainty associated to different aspects of RST modeling. In a predictive setting, one frequently encounters an absence of any relevant reference data. To make data-free predictions with quantified uncertainty we employ physical bounds to a-priori define maximum spectral perturbations. When propagated, these perturbations yield intervals of engineering utility. High-fidelity data opens up the possibility of inferring a distribution of uncertainty, by means of various data-driven machine-learning techniques. We will demonstrate our framework on a number of flow problems where RANS models are prone to failure. This research was partially supported by the Defense Advanced Research Projects Agency under the Enabling Quantification of Uncertainty in Physical Systems (EQUiPS) project (technical monitor: Dr Fariba Fahroo), and the DOE PSAAP-II program.

Nanoparticle-mediated nonclassical crystal growth of sodium fluorosilicate nanowires and nanoplates

Directory of Open Access Journals (Sweden)

Hongxia Li

2011-12-01

Full Text Available We observed nonclassical crystal growth of the sodium fluorosilicate nanowires, nanoplates, and hierarchical structures through self-assembly and aggregation of primary intermediate nanoparticles. Unlike traditional ion-by-ion crystallization, the primary nanoparticles formed first and their subsequent self-assembly, fusion, and crystallization generated various final crystals. These findings offer direct evidences for the aggregation-based crystallization mechanism.

Discriminating strength: a bona fide measure of non-classical correlations

Science.gov (United States)

Farace, A.; De Pasquale, A.; Rigovacca, L.; Giovannetti, V.

2014-07-01

A new measure of non-classical correlations is introduced and characterized. It tests the ability of using a state ρ of a composite system AB as a probe for a quantum illumination task (e.g. see Lloyd 2008 Science 321 1463), in which one is asked to remotely discriminate between the two following scenarios: (i) either nothing happens to the probe, or (ii) the subsystem A is transformed via a local unitary {{R}_{A}} whose properties are partially unspecified when producing ρ. This new measure can be seen as the discrete version of the recently introduced interferometric power measure (Girolami et al 2013 e-print arXiv:1309.1472) and, at least for the case in which A is a qubit, it is shown to coincide (up to an irrelevant scaling factor) with the local quantum uncertainty measure of Girolami, Tufarelli and Adesso (2013 Phys. Rev. Lett. 110 240402). Analytical expressions are derived which allow us to formally prove that, within the set of separable configurations, the maximum value of our non-classicality measure is achieved over the set of quantum-classical states (i.e. states ρ which admit a statistical unravelling where each element of the associated ensemble is distinguishable via local measures on B).

Discriminating strength: a bona fide measure of non-classical correlations

Energy Technology Data Exchange (ETDEWEB)

Farace, A; De Pasquale, A; Giovannetti, V [NEST, Scuola Normale Superiore and Istituto Nanoscienze-CNR, I-56126 Pisa (Italy); Rigovacca, L [Scuola Normale Superiore, I-56126 Pisa (Italy)

2014-07-01

A new measure of non-classical correlations is introduced and characterized. It tests the ability of using a state ρ of a composite system AB as a probe for a quantum illumination task (e.g. see Lloyd 2008 Science 321 1463), in which one is asked to remotely discriminate between the two following scenarios: (i) either nothing happens to the probe, or (ii) the subsystem A is transformed via a local unitary R{sub A} whose properties are partially unspecified when producing ρ. This new measure can be seen as the discrete version of the recently introduced interferometric power measure (Girolami et al 2013 e-print arXiv:1309.1472) and, at least for the case in which A is a qubit, it is shown to coincide (up to an irrelevant scaling factor) with the local quantum uncertainty measure of Girolami, Tufarelli and Adesso (2013 Phys. Rev. Lett. 110 240402). Analytical expressions are derived which allow us to formally prove that, within the set of separable configurations, the maximum value of our non-classicality measure is achieved over the set of quantum-classical states (i.e. states ρ which admit a statistical unravelling where each element of the associated ensemble is distinguishable via local measures on B). (paper)

Discriminating strength: a bona fide measure of non-classical correlations

International Nuclear Information System (INIS)

Farace, A; De Pasquale, A; Giovannetti, V; Rigovacca, L

2014-01-01

A new measure of non-classical correlations is introduced and characterized. It tests the ability of using a state ρ of a composite system AB as a probe for a quantum illumination task (e.g. see Lloyd 2008 Science 321 1463), in which one is asked to remotely discriminate between the two following scenarios: (i) either nothing happens to the probe, or (ii) the subsystem A is transformed via a local unitary R A whose properties are partially unspecified when producing ρ. This new measure can be seen as the discrete version of the recently introduced interferometric power measure (Girolami et al 2013 e-print arXiv:1309.1472) and, at least for the case in which A is a qubit, it is shown to coincide (up to an irrelevant scaling factor) with the local quantum uncertainty measure of Girolami, Tufarelli and Adesso (2013 Phys. Rev. Lett. 110 240402). Analytical expressions are derived which allow us to formally prove that, within the set of separable configurations, the maximum value of our non-classicality measure is achieved over the set of quantum-classical states (i.e. states ρ which admit a statistical unravelling where each element of the associated ensemble is distinguishable via local measures on B). (paper)

Hybrid RANS/LES of flow and heat transfer in round impinging jets

International Nuclear Information System (INIS)

Kubacki, Slawomir; Dick, Erik

2011-01-01

Fluid flow and convective heat transfer predictions are presented of round impinging jets for several combinations of nozzle-plate distances H/D = 2, 6 and 13.5 (where D is the nozzle diameter) and Reynolds numbers Re = 5000, 23,000 and 70,000 with the newest version of the k-ω model of and three hybrid RANS/LES models. In the RANS mode of the hybrid RANS/LES models, the k-ω model is recovered. Three formulations are considered to activate the LES mode. The first model is similar to the hybrid models of and . The turbulent length scale is replaced by the grid size in the destruction term of the k-equation and in the definition of the RANS eddy viscosity. As grid size, a maximum measure of the hexahedral grid cell is used. The second model has the same k-equation, but the eddy viscosity is the minimum of the k-ω eddy viscosity and the Smagorinsky eddy viscosity, following a proposal by . The Smagorinsky eddy viscosity is formed with the cube root of the cell volume. The third model has, again, the same k-equation, but has an eddy viscosity which is an intermediate between the eddy viscosities of the first and second models. This is reached by using the cube root of the cell volume in the eddy viscosity formula of the first model. The simulation results are compared with experimental data for the high Reynolds number cases Re = 23,000 and Re = 70,000 and LES data for the low-Reynolds number case Re = 5000. The Reynolds numbers are defined with the nozzle diameter and the bulk velocity at nozzle outlet. At low nozzle-plate distance (the impingement plate is in the core of the jet), turbulent kinetic energy is overpredicted by RANS in the stagnation flow region. This leads to overprediction of the heat transfer rate along the impingement plate in the impact zone. At high nozzle-plate distance (the impingement plate is in the mixed-out region of the jet), the turbulence mixing is underpredicted by RANS in the shear layer of the jet which gives a too high length of

The Inner Nuclear Membrane Protein Nemp1 Is a New Type of RanGTP-Binding Protein in Eukaryotes.

Directory of Open Access Journals (Sweden)

Takashi Shibano

Full Text Available The inner nuclear membrane (INM protein Nemp1/TMEM194A has previously been suggested to be involved in eye development in Xenopus, and contains two evolutionarily conserved sequences in the transmembrane domains (TMs and the C-terminal region, named region A and region B, respectively. To elucidate the molecular nature of Nemp1, we analyzed its interacting proteins through those conserved regions. First, we found that Nemp1 interacts with itself and lamin through the TMs and region A, respectively. Colocalization of Nemp1 and lamin at the INM suggests that the interaction with lamin participates in the INM localization of Nemp1. Secondly, through yeast two-hybrid screening using region B as bait, we identified the small GTPase Ran as a probable Nemp1-binding partner. GST pulldown and co-immunoprecipitation assays using region B and Ran mutants revealed that region B binds directly to the GTP-bound Ran through its effector domain. Immunostaining experiments using transfected COS-7 cells revealed that full-length Nemp1 recruits Ran near the nuclear envelope, suggesting a role for Nemp1 in the accumulation of RanGTP at the nuclear periphery. At the neurula-to-tailbud stages of Xenopus embryos, nemp1 expression overlapped with ran in several regions including the eye vesicles. Co-knockdown using antisense morpholino oligos for nemp1 and ran caused reduction of cell densities and severe eye defects more strongly than either single knockdown alone, suggesting their functional interaction. Finally we show that Arabidopsis thaliana Nemp1-orthologous proteins interact with A. thaliana Ran, suggesting their evolutionally conserved physical and functional interactions possibly in basic cellular functions including nuclear transportation. Taken together, we conclude that Nemp1 represents a new type of RanGTP-binding protein.

Immunomodulation of classical and non-classical HLA molecules by ionizing radiation.

Science.gov (United States)

Gallegos, Cristina E; Michelin, Severino; Dubner, Diana; Carosella, Edgardo D

2016-05-01

Radiotherapy has been employed for the treatment of oncological patients for nearly a century, and together with surgery and chemotherapy, radiation oncology constitutes one of the three pillars of cancer therapy. Ionizing radiation has complex effects on neoplastic cells and on tumor microenvironment: beyond its action as a direct cytotoxic agent, tumor irradiation triggers a series of alterations in tumoral cells, which includes the de novo synthesis of particular proteins and the up/down-regulation of cell surface molecules. Additionally, ionizing radiation may induce the release of "danger signals" which may, in turn lead to cellular and molecular responses by the immune system. This immunomodulatory action of ionizing radiation highlights the importance of the combined use (radiotherapy plus immunotherapy) for cancer healing. Major histocompatibility complex antigens (also called Human Leukocyte Antigens, HLA in humans) are one of those molecules whose expression is modulated after irradiation. This review summarizes the modulatory properties of ionizing radiation on the expression of HLA class I (classical and non-classical) and class II molecules, with special emphasis in non-classical HLA-I molecules. Copyright © 2016 Elsevier Inc. All rights reserved.

Nonclassical Ly6C− Monocytes Drive the Development of Inflammatory Arthritis in Mice

Directory of Open Access Journals (Sweden)

Alexander V. Misharin

2014-10-01

Full Text Available Different subsets and/or polarized phenotypes of monocytes and macrophages may play distinct roles during the development and resolution of inflammation. Here, we demonstrate in a murine model of rheumatoid arthritis that nonclassical Ly6C− monocytes are required for the initiation and progression of sterile joint inflammation. Moreover, nonclassical Ly6C− monocytes differentiate into inflammatory macrophages (M1, which drive disease pathogenesis and display plasticity during the resolution phase. During the development of arthritis, these cells polarize toward an alternatively activated phenotype (M2, promoting the resolution of joint inflammation. The influx of Ly6C− monocytes and their subsequent classical and then alternative activation occurs without changes in synovial tissue-resident macrophages, which express markers of M2 polarization throughout the course of the arthritis and attenuate joint inflammation during the initiation phase. These data suggest that circulating Ly6C− monocytes recruited to the joint upon injury orchestrate the development and resolution of autoimmune joint inflammation.

İRAN VE REJİM İSTİKRARI

Directory of Open Access Journals (Sweden)

Özgür ÜŞENMEZ

2015-07-01

Full Text Available ÖZ: Bu çalışma, İran rejiminin son yıllarda Orta Doğu'yu sarsan isyanlar ve istikrarsızlıklara-Batı'daki beklentilerin aksine- geçmişten, özellikle 1979'daki devrimden miras kalan sosyal yapı ve politikaların etkisiyle direnebildiğini iddia ediyor. Tunus ve Mısır'daki halk isyanları, temel aktör olan alt sınıflar ve onların neo-liberal ekonomik politikalara muhalefetiyle yayılırken, İran’da devrim sonrası gelişen sosyal devlet mekanizması hala halk ile rejimin tamamen birbirine yabancılaşmasını önlemekte. Ancak son yıllarda ortaya çıkan yeni gerilimler ve İran'ın uyguladığı ekonomi politikaları rejimin krizini derinleştirebilir. Bu nedenledir ki Orta Doğu'yu ve özelde İran'ı anlamak için hegemonik blokların tarihsel değişimini inceleyen ucu açık bir analiz elzemdir. ABSTRACT: This article argues that contrary to the expectations of the Western World, Iranian regime successfully resisted the revolutionary tides of the Arab Spring. Most important determinant of this process for Iran was the legacy of the 1979 revolution and it's associated structures that relatively protects the most vulnerable parts of the population against the wide spread neo-liberal economic policies in the Middle East. So with that feature Iran differs from the Tunisian and the Egyptian examples. In order to understand these features further this essay adapts a historical analysis of changes in hegemonic blocs in Iran since 1979.

Involvement of caspase-dependent and -independent apoptotic pathways in cisplatin-induced apoptosis

Science.gov (United States)

Liu, Lei; Zhang, Yingjie; Wang, Xianwang

2009-02-01

Cisplatin, an efficient anticancer agent, can trigger multiple apoptotic pathways in cancer cells. However, the signal transduction pathways in response to cisplatin-based chemotherapy are complicated, and the mechanism is not fully understood. In current study, we showed that, during cisplatin-induced apoptosis of human lung adenocarcinoma cells, both the caspase-dependent and -independent pathways were activated. Herein, we reported that after cisplatin treatment, the activities of caspase-9/-3 were sharply increased; pre-treatment with Z-LEHD-fmk (inhibitor of caspase-9), Z-DEVD-fmk (inhibitor of caspase-3), and Z-VAD-fmk (a pan-caspase inhibitor) increased cell viability and decreased apoptosis, suggesting that caspase-mediated apoptotic pathway was activated following cisplatin treatment. Confocal imaging of the cells transfected with AIF-GFP demonstrated that AIF release occurred about 9 h after cisplatin treatment. The event proceeded progressively over time, coinciding with a nuclear translocation and lasting for more than 2 hours. Down-regulation of AIF by siRNA also significantly increased cell viability and decreased apoptosis, these results suggested that AIF-mediated caspase-independent apoptotic pathway was involved in cispatin-induced apoptosis. In conclusion, the current study demonstrated that both caspase-dependent and -independent apoptotic pathways were involved in cisplatin-induced apoptosis in human lung adenocarcinoma cells.

Optimal Assignment of Cells in C-RAN Deployments with Multiple BBU Pools

DEFF Research Database (Denmark)

Holm, Henrik; Checko, Aleksandra; Al-obaidi, Rami

2015-01-01

Cloud Radio Access Network (C-RAN) is receiving increasing attention not only within the research community but also from operators and standardization bodies. However, even a good technology will be deployed only if it is economically viable. In our previous work, for larger scale deployment we...... recommend to divide the area into multiple BBU Pools. In this paper we show how to optimally assign cells to different BBU Pools in such a scenario. By using Integer Linear Programming (ILP) method we derive engineering guidelines for minimizing the CAPital EXpenditure (CAPEX) of C-RAN deployment....

Joint probability distributions of stimulated parametric down-conversion for controllable nonclassical fluctuations

Czech Academy of Sciences Publication Activity Database

Peřina, Jan; Křepelka, Jaromír

2008-01-01

Roč. 281, č. 18 (2008), s. 4705-4711 ISSN 0030-4018 R&D Projects: GA AV ČR IAA100100713; GA MŠk(CZ) 1M06002 Institutional research plan: CEZ:AV0Z10100522 Keywords : quantum measurement * parametric down-conversion * nonclassical light * quantum noise Subject RIV: BH - Optics, Masers, Lasers Impact factor: 1.552, year: 2008

Brain Pathways to Recovery from Alcohol Dependence

Science.gov (United States)

Cui, Changhai; Noronha, Antonio; Warren, Kenneth; Koob, George F.; Sinha, Rajita; Thakkar, Mahesh; Matochik, John; Crews, Fulton T.; Chandler, L. Judson; Pfefferbaum, Adolf; Becker, Howard C.; Lovinger, David; Everitt, Barry; Egli, Mark; Mandyam, Chitra; Fein, George; Potenza, Marc N.; Harris, R. Adron; Grant, Kathleen A.; Roberto, Marisa; Meyerhoff, Dieter J.; Sullivan, Edith V.

2015-01-01

This article highlights the research presentations at the satellite symposium on “Brain Pathways to Recovery from Alcohol Dependence” held at the 2013 Society for Neuroscience Annual Meeting. The purpose of this symposium was to provide an up to date overview of research efforts focusing on understanding brain mechanisms that contribute to recovery from alcohol dependence. A panel of scientists from the alcohol and addiction research field presented their insights and perspectives on brain mechanisms that may underlie both recovery and lack of recovery from alcohol dependence. The four sessions of the symposium encompassed multilevel studies exploring mechanisms underlying relapse and craving associated with sustained alcohol abstinence, cognitive function deficit and recovery, and translational studies on preventing relapse and promoting recovery. Gaps in our knowledge and research opportunities were also discussed. PMID:26074423

EFFECTS OF PARAMETRIC VARIATIONS ON SEISMIC ANALYSIS METHODS FOR NON-CLASSICALLY DAMPED COUPLED SYSTEMS

International Nuclear Information System (INIS)

XU, J.; DEGRASSI, G.

2000-01-01

A comprehensive benchmark program was developed by Brookhaven National Laboratory (BNL) to perform an evaluation of state-of-the-art methods and computer programs for performing seismic analyses of coupled systems with non-classical damping. The program, which was sponsored by the US Nuclear Regulatory Commission (NRC), was designed to address various aspects of application and limitations of these state-of-the-art analysis methods to typical coupled nuclear power plant (NPP) structures with non-classical damping, and was carried out through analyses of a set of representative benchmark problems. One objective was to examine the applicability of various analysis methods to problems with different dynamic characteristics unique to coupled systems. The examination was performed using parametric variations for three simple benchmark models. This paper presents the comparisons and evaluation of the program participants' results to the BNL exact solutions for the applicable ranges of modeling dynamic characteristic parameters

Phase-space representation of non-classical behaviour of scalar wave-fields

International Nuclear Information System (INIS)

Canas-Cardona, Gustavo; Castaneda, Roman; Vinck-Posada, Herbert

2011-01-01

The modelling of optical fields by using radiant and virtual point sources for the spatial coherence wavelets in the phase-space representation evidences some effects, conventionally attributed to non-classical correlations of light, although such type of correlations are not explicitly included in the model. Specifically, a light state is produced that has similar morphology to the Wigner Distribution Function of the well-known quantum Schroedinger cat and squeezed states.

Qubit-oscillator systems in the ultrastrong-coupling regime and their potential for preparing nonclassical states

Science.gov (United States)

Nori, Franco; Ashhab, Sahel

2011-03-01

We consider a system composed of a two-level system (i.e. a qubit) and a harmonic oscillator in the ultrastrong-coupling regime, where the coupling strength is comparable to the qubit and oscillator energy scales. We explore the possibility of preparing nonclassical states in this system, especially in the ground state of the combined system. The nonclassical states that we consider include squeezed states, Schrodinger-cat states and entangled states. We also analyze the nature of the change in the ground state as the coupling strength is increased, going from a separable ground state in the absence of coupling to a highly entangled ground state in the case of very strong coupling. Reference: S. Ashhab and F. Nori, Phys. Rev. A 81, 042311 (2010). We thank support from DARPA, AFOSR, NSA, LPS, ARO, NSF, MEXT, JSPS, FIRST, and JST.

Nanoformulation of D-α-tocopheryl polyethylene glycol 1000 succinate-b-poly(ε-caprolactone-ran-glycolide) diblock copolymer for breast cancer therapy.

Science.gov (United States)

Huang, Laiqiang; Chen, Hongbo; Zheng, Yi; Song, Xiaosong; Liu, Ranyi; Liu, Kexin; Zeng, Xiaowei; Mei, Lin

2011-10-01

The purpose of this research was to develop formulation of docetaxel-loaded biodegradable TPGS-b-(PCL-ran-PGA) nanoparticles for breast cancer chemotherapy. A novel diblock copolymer, d-α-tocopheryl polyethylene glycol 1000 succinate-b-poly(ε-caprolactone-ran-glycolide) [TPGS-b-(PCL-ran-PGA)], was synthesized from ε-caprolactone, glycolide and d-α-tocopheryl polyethylene glycol 1000 succinate by ring-opening polymerization using stannous octoate as catalyst. The obtained copolymers were characterized by (1)H NMR, GPC and TGA. The docetaxel-loaded TPGS-b-(PCL-ran-PGA) nanoparticles were prepared and characterized. The data showed that the fluorescence TPGS-b-(PCL-ran-PGA) nanoparticles could be internalized by MCF-7 cells. The TPGS-b-(PCL-ran-PGA) nanoparticles achieved significantly higher level of cytotoxicity than commercial Taxotere®. MCF-7 xenograft tumor model on SCID mice showed that docetaxel formulated in the TPGS-b-(PCL-ran-PGA) nanoparticles could effectively inhibit the growth of tumor over a longer period of time than Taxotere® at the same dose. In conclusion, the TPGS-b-(PCL-ran-PGA) copolymer could be acted as a novel and potential biologically active polymeric material for nanoformulation in breast cancer chemotherapy. This journal is © The Royal Society of Chemistry 2011

The prognostic role of classical and nonclassical MHC class I expression in endometrial cancer

NARCIS (Netherlands)

Bijen, C.B.; Bantema-Joppe, E.J.; de Jong, Renske; Leffers, N.; Mourits, M.J.; Eggink, Henk F.; van der Zee, A.G.; Hollema, H.; de Bock, G.H.; Nijman, H.W.

2010-01-01

The aim of this study was to investigate classical MHC class I and nonclassical MHC (human leukocyte antigen-G [HLA-GJ) expression in a large cohort of patients with endometrial cancer, to determine the prognostic value of these cell surface markers and their relation with clinicopathological

Squeezing, photon bunching, photon antibunching and nonclassical photon statistics in degenerate hyper Raman processes

International Nuclear Information System (INIS)

Sen, Biswajit; Mandal, Swapan

2007-01-01

An initially prepared coherent state coupled to a second-order nonlinear medium is responsible for stimulated and spontaneous hyper Raman processes. By using an intuitive approach based on perturbation theory, the Hamiltonian corresponding to the hyper Raman processes is analytically solved to obtain the temporal development of the field operators. It is true that these analytical solutions are valid for small coupling constants. However, the interesting part is that these solutions are valid for reasonably large time. Hence, the present analytical solutions are quite general and are fresh compared to those solutions under short-time approximations. By exploiting the analytical solutions of field operators for various modes, we investigate the squeezing, photon antibunching and nonclassical photon statistics for pure modes of the input coherent light responsible for hyper Raman processes. At least in one instance (stimulated hyper Raman processes for vibration phonon mode), we report the simultaneous appearance of classical (photon bunching) and nonclassical (squeezing) effects of the radiation field responsible for hyper Raman processes

Overview on methods for formulating explicit damping matrices for non-classically damped structures

International Nuclear Information System (INIS)

Xu, J.

1998-04-01

In computing the dynamic response of a connected system with multiple components having dissimilar damping characteristics, which is often referred to as nonclassically damped system such as nuclear power plant piping systems supported by stiff structures, one needs to define the system-level damping based upon the damping information of components. This is frequently done in practice using approximate methods expressed as composite modal damping with weighting functions. However, when the difference in damping among components is substantial, the composite modal damping may become inappropriate in the characterization of the damping behavior of such systems. In recent years, several new methods have emerged with the expectation that they could produce more exact system-level damping for a group of nonclassically damped structures which are comprised of components that possess classical modal damping. In this paper, an overview is presented to examine these methods in the light of their theoretical basis, the technical merits, and practical applications. To this end, a synthesis method is described, which was shown to reduce to the other methods in the literature

Dependency of climate change and carbon cycle on CO2 emission pathways

International Nuclear Information System (INIS)

Nohara, Daisuke; Yoshida, Yoshikatsu; Misumi, Kazuhiro; Ohba, Masamichi

2013-01-01

Previous research has indicated that the response of globally average temperature is approximately proportional to cumulative CO 2 emissions, yet evidence of the robustness of this relationship over a range of CO 2 emission pathways is lacking. To address this, we evaluate the dependency of climate and carbon cycle change on CO 2 emission pathways using a fully coupled climate–carbon cycle model. We design five idealized pathways (including an overshoot scenario for cumulative emissions), each of which levels off to final cumulative emissions of 2000 GtC. The cumulative emissions of the overshoot scenario reach 4000 GtC temporarily, subsequently reducing to 2000 GtC as a result of continuous negative emissions. Although we find that responses of climatic variables and the carbon cycle are largely independent of emission pathways, a much weakened Atlantic meridional overturning circulation (AMOC) is projected in the overshoot scenario despite cessation of emissions. This weakened AMOC is enhanced by rapid warming in the Arctic region due to considerable temporary elevation of atmospheric CO 2 concentration and induces the decline of surface air temperature and decrease of precipitation over the northern Atlantic and Europe region. Moreover, the weakened AMOC reduces CO 2 uptake by the Atlantic and Arctic oceans. However, the weakened AMOC contributes little to the global carbon cycle. In conclusion, although climate variations have been found to be dependent on emission pathways, the global carbon cycle is relatively independent of these emission pathways, at least superficially. (letter)

Assessment of RANS and LES Turbulence Modeling for Buoyancy-Aided/Opposed Forced and Mixed Convection

Science.gov (United States)

Clifford, Corey; Kimber, Mark

2017-11-01

Over the last 30 years, an industry-wide shift within the nuclear community has led to increased utilization of computational fluid dynamics (CFD) to supplement nuclear reactor safety analyses. One such area that is of particular interest to the nuclear community, specifically to those performing loss-of-flow accident (LOFA) analyses for next-generation very-high temperature reactors (VHTR), is the capacity of current computational models to predict heat transfer across a wide range of buoyancy conditions. In the present investigation, a critical evaluation of Reynolds-averaged Navier-Stokes (RANS) and large-eddy simulation (LES) turbulence modeling techniques is conducted based on CFD validation data collected from the Rotatable Buoyancy Tunnel (RoBuT) at Utah State University. Four different experimental flow conditions are investigated: (1) buoyancy-aided forced convection; (2) buoyancy-opposed forced convection; (3) buoyancy-aided mixed convection; (4) buoyancy-opposed mixed convection. Overall, good agreement is found for both forced convection-dominated scenarios, but an overly-diffusive prediction of the normal Reynolds stress is observed for the RANS-based turbulence models. Low-Reynolds number RANS models perform adequately for mixed convection, while higher-order RANS approaches underestimate the influence of buoyancy on the production of turbulence.

Evaluation of Packet Preemption over C-RAN Fronthaul Networks

DEFF Research Database (Denmark)

Yan, Ying; Zhou, Zifan; Ruepp, Sarah Renée

2017-01-01

The Cloud Radio Access Network (C-RAN) is viewed as a new solution with benefits of reduced cost by sharing resources. This is achieved by the separation of the radio part and the radio processing part, where the transport network between them is referred to as front-haul. It is essential to meet...

In situ SUMOylation analysis reveals a modulatory role of RanBP2 in the nuclear rim and PML bodies

International Nuclear Information System (INIS)

Saitoh, Noriko; Uchimura, Yasuhiro; Tachibana, Taro; Sugahara, Satoko; Saitoh, Hisato; Nakao, Mitsuyoshi

2006-01-01

SUMO modification plays a critical role in a number of cellular functions including nucleocytoplasmic transport, gene expression, cell cycle and formation of subnuclear structures such as promyelocytic leukemia (PML) bodies. In order to identify the sites where SUMOylation takes place in the cell, we developed an in situ SUMOylation assay using a semi-intact cell system and subsequently combined it with siRNA-based knockdown of nucleoporin RanBP2, also known as Nup358, which is one of the known SUMO E3 proteins. With the in situ SUMOylation assay, we found that both nuclear rim and PML bodies, besides mitotic apparatuses, are major targets for active SUMOylation. The ability to analyze possible SUMO conjugation sites would be a valuable tool to investigate where SUMO E3-like activities and/or SUMO substrates exist in the cell. Specific knockdown of RanBP2 completely abolished SUMOylation along the nuclear rim and dislocated RanGAP1 from the nuclear pore complexes. Interestingly, the loss of RanBP2 markedly reduced the number of PML bodies, in contrast to other, normal-appearing nuclear compartments including the nuclear lamina, nucleolus and chromatin, suggesting a novel link between RanBP2 and PML bodies. SUMOylation facilitated by RanBP2 at the nuclear rim may be a key step for the formation of a particular subnuclear organization. Our data imply that SUMO E3 proteins like RanBP2 facilitate spatio-temporal SUMOylation for certain nuclear structure and function

[Taxonomic theory for non-classical systematics].

Science.gov (United States)

Pavlinov, I Ia

2012-01-01

Outlined briefly are basic principles of construing general taxonomic theory for biological systematics considered in the context of non-classical scientific paradigm. The necessity of such kind of theory is substantiated, and some key points of its elaboration are exposed: its interpretation as a framework concept for the partial taxonomic theories in various schools of systematics; elaboration of idea of cognitive situation including three interrelated components, namely subject, object, and epistemic ones; its construing as a content-wisely interpreted quasi-axiomatics, with strong structuring of its conceptual space including demarcation between axioms and inferring rules; its construing as a "conceptual pyramid" of concepts of various levels of generality; inclusion of a basic model into definition of the taxonomic system (classification) regulating its content. Two problems are indicated as fundamental: definition of taxonomic diversity as a subject domain for the systematics as a whole; definition of onto-epistemological status of taxonomic system (classification) in general and of taxa in particular.

P2X7 receptors regulate multiple types of membrane trafficking responses and non-classical secretion pathways.

Science.gov (United States)

Qu, Yan; Dubyak, George R

2009-06-01

Activation of the P2X7 receptor (P2X7R) triggers a remarkably diverse array of membrane trafficking responses in leukocytes and epithelial cells. These responses result in altered profiles of cell surface lipid and protein composition that can modulate the direct interactions of P2X7R-expressing cells with other cell types in the circulation, in blood vessels, at epithelial barriers, or within sites of immune and inflammatory activation. Additionally, these responses can result in the release of bioactive proteins, lipids, and large membrane complexes into extracellular compartments for remote communication between P2X7R-expressing cells and other cells that amplify or modulate inflammation, immunity, and responses to tissue damages. This review will discuss P2X7R-mediated effects on membrane composition and trafficking in the plasma membrane (PM) and intracellular organelles, as well as actions of P2X7R in controlling various modes of non-classical secretion. It will review P2X7R regulation of: (1) phosphatidylserine distribution in the PM outer leaflet; (2) shedding of PM surface proteins; (3) release of PM-derived microvesicles or microparticles; (4) PM blebbing; (5) cell-cell fusion resulting in formation of multinucleate cells; (6) phagosome maturation and fusion with lysosomes; (7) permeability of endosomes with internalized pathogen-associated molecular patterns; (8) permeability/integrity of mitochondria; (9) exocytosis of secretory lysosomes; and (10) release of exosomes from multivesicular bodies.

Expression of bovine non-classical major histocompatibility complex class I proteins in mouse P815 and human K562 cells.

Science.gov (United States)

Parasar, Parveen; Wilhelm, Amanda; Rutigliano, Heloisa M; Thomas, Aaron J; Teng, Lihong; Shi, Bi; Davis, William C; Suarez, Carlos E; New, Daniel D; White, Kenneth L; Davies, Christopher J

2016-08-01

Major histocompatibility complex class I (MHC-I) proteins can be expressed as cell surface or secreted proteins. To investigate whether bovine non-classical MHC-I proteins are expressed as cell surface or secreted proteins, and to assess the reactivity pattern of monoclonal antibodies with non-classical MHC-I isoforms, we expressed the MHC proteins in murine P815 and human K562 (MHC-I deficient) cells. Following antibiotic selection, stably transfected cell lines were stained with H1A or W6/32 antibodies to detect expression of the MHC-I proteins by flow cytometry. Two non-classical proteins (BoLA-NC1*00501 and BoLA-NC3*00101) were expressed on the cell surface in both cell lines. Surprisingly, the BoLA-NC4*00201 protein was expressed on the cell membrane of human K562 but not mouse P815 cells. Two non-classical proteins (BoLA-NC1*00401, which lacks a transmembrane domain, and BoLA-NC2*00102) did not exhibit cell surface expression. Nevertheless, Western blot analyses demonstrated expression of the MHC-I heavy chain in all transfected cell lines. Ammonium-sulfate precipitation of proteins from culture supernatants showed that BoLA-NC1*00401 was secreted and that all surface expressed proteins where shed from the cell membrane by the transfected cells. Interestingly, the surface expressed MHC-I proteins were present in culture supernatants at a much higher concentration than BoLA-NC1*00401. This comprehensive study shows that bovine non-classical MHC-I proteins BoLA-NC1*00501, BoLA-NC3*00101, and BoLA-NC4*00201 are expressed as surface isoforms with the latter reaching the cell membrane only in K562 cells. Furthermore, it demonstrated that BoLA-NC1*00401 is a secreted isoform and that significant quantities of membrane associated MHC-I proteins can be shed from the cell membrane. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Identification and estimation of nonlinear models using two samples with nonclassical measurement errors

KAUST Repository

Carroll, Raymond J.

2010-05-01

This paper considers identification and estimation of a general nonlinear Errors-in-Variables (EIV) model using two samples. Both samples consist of a dependent variable, some error-free covariates, and an error-prone covariate, for which the measurement error has unknown distribution and could be arbitrarily correlated with the latent true values; and neither sample contains an accurate measurement of the corresponding true variable. We assume that the regression model of interest - the conditional distribution of the dependent variable given the latent true covariate and the error-free covariates - is the same in both samples, but the distributions of the latent true covariates vary with observed error-free discrete covariates. We first show that the general latent nonlinear model is nonparametrically identified using the two samples when both could have nonclassical errors, without either instrumental variables or independence between the two samples. When the two samples are independent and the nonlinear regression model is parameterized, we propose sieve Quasi Maximum Likelihood Estimation (Q-MLE) for the parameter of interest, and establish its root-n consistency and asymptotic normality under possible misspecification, and its semiparametric efficiency under correct specification, with easily estimated standard errors. A Monte Carlo simulation and a data application are presented to show the power of the approach.

Direct experimental observation of nonclassicality in ensembles of single-photon emitters

Science.gov (United States)

Moreva, E.; Traina, P.; Forneris, J.; Degiovanni, I. P.; Ditalia Tchernij, S.; Picollo, F.; Brida, G.; Olivero, P.; Genovese, M.

2017-11-01

In this work we experimentally demonstrate a recently proposed criterion addressed to detect nonclassical behavior in the fluorescence emission of ensembles of single-photon emitters. In particular, we apply the method to study clusters of nitrogen-vacancy centers in diamond characterized with single-photon-sensitive confocal microscopy. Theoretical considerations on the behavior of the parameter at any arbitrary order in the presence of Poissonian noise are presented and, finally, the opportunity of detecting manifold coincidences is discussed.

Phase-dependent quantum interference between different pathways in bichromatic harmonic generation

International Nuclear Information System (INIS)

Jun, Cai; Li-Ming, Wang; Hao-Xue, Qiao

2009-01-01

This paper studies the harmonic generation of the hydrogen atom subjected to a collinear bichromatic laser field by numerically solving the time-dependent Schrödinger equation using the split-operator pseudo-spectral method. By adding a frequency variation to the additional field, the contributions of different pathways to particular order harmonic generation can be isolated. The quantum interference pattern between harmonic pathways, which influences the harmonic intensity, is found to be either constructive or destructive with respect to different relative phase of the two field components. Detailed description of up to the 35th-order harmonics and the harmonic pathways for a wide range of field parameters is presented. (atomic and molecular physics)

Metformin downregulates the insulin/IGF-I signaling pathway and inhibits different uterine serous carcinoma (USC) cells proliferation and migration in p53-dependent or -independent manners.

Science.gov (United States)

Sarfstein, Rive; Friedman, Yael; Attias-Geva, Zohar; Fishman, Ami; Bruchim, Ilan; Werner, Haim

2013-01-01

Accumulating epidemiological evidence shows that obesity is associated with an increased risk of several types of adult cancers, including endometrial cancer. Chronic hyperinsulinemia, a typical hallmark of diabetes, is one of the leading factors responsible for the obesity-cancer connection. Numerous cellular and circulating factors are involved in the biochemical chain of events leading from hyperinsulinemia and insulin resistance to increased cancer risk and, eventually, tumor development. Metformin is an oral anti-diabetic drug of the biguanide family used for treatment of type 2 diabetes. Recently, metformin was shown to exhibit anti-proliferative effects in ovarian and Type I endometrial cancer, although the mechanisms responsible for this non-classical metformin action remain unclear. The insulin-like growth factors (IGFs) play a prominent role in cancer biology and their mechanisms of action are tightly interconnected with the insulin signaling pathways. Given the cross-talk between the insulin and IGF signaling pathways, the aim of this study was to examine the hypothesis that the anti-proliferative actions of metformin in uterine serous carcinoma (USC) are potentially mediated via suppression of the IGF-I receptor (IGF-IR) pathway. Our results show that metformin interacts with the IGF pathway, and induces apoptosis and inhibition of proliferation and migration of USC cell lines with both wild type and mutant p53. Taken together, our results suggest that metformin therapy could be a novel and attractive therapeutic approach for human USC, a highly aggressive variant of endometrial cancer.

Improved CORF model of simple cell combined with non-classical receptive field and its application on edge detection

Science.gov (United States)

Sun, Xiao; Chai, Guobei; Liu, Wei; Bao, Wenzhuo; Zhao, Xiaoning; Ming, Delie

2018-02-01

Simple cells in primary visual cortex are believed to extract local edge information from a visual scene. In this paper, inspired by different receptive field properties and visual information flow paths of neurons, an improved Combination of Receptive Fields (CORF) model combined with non-classical receptive fields was proposed to simulate the responses of simple cell's receptive fields. Compared to the classical model, the proposed model is able to better imitate simple cell's physiologic structure with consideration of facilitation and suppression of non-classical receptive fields. And on this base, an edge detection algorithm as an application of the improved CORF model was proposed. Experimental results validate the robustness of the proposed algorithm to noise and background interference.

Molecular characterization of classical and nonclassical MHC class I genes from the golden pheasant (Chrysolophus pictus).

Science.gov (United States)

Zeng, Q-Q; Zhong, G-H; He, K; Sun, D-D; Wan, Q-H

2016-02-01

Classical major histocompatibility complex (MHC) class I allelic polymorphism is essential for competent antigen presentation. To improve the genotyping efforts in the golden pheasant, it is necessary to differentiate more accurately between classical and nonclassical class I molecules. In our study, all MHC class I genes were isolated from one golden pheasant based on two overlapping PCR amplifications. In total, six full-length class I nucleotide sequences (A-F) were identified, and four were novel. Two (A and C) belonged to the IA1 gene, two (B and D) were alleles derived from the IA2 gene through transgene amplification, and two (E and F) comprised a third novel locus, IA3 that was excluded from the core region of the golden pheasant MHC-B. IA1 and IA2 exhibited the broad expression profiles characteristic of classical loci, while IA3 showed no expression in multiple tissues and was therefore defined as a nonclassical gene. Phylogenetic analysis indicated that the three IA genes in the golden pheasant share a much closer evolutionary relationship than the corresponding sequences in other galliform species. This observation was consistent with high sequence similarity among them, which likely arises from the homogenizing effect of recombination. Our careful distinction between the classical and nonclassical MHC class I genes in the golden pheasant lays the foundation for developing locus-specific genotyping and establishing a good molecular marker system of classical MHC I loci. © 2015 John Wiley & Sons Ltd.

Nonclassicality and decoherence of photon-added squeezed coherent Schrödinger kitten states in a Kerr medium

Science.gov (United States)

Chakrabarti, R.; Yogesh, V.

2018-01-01

We study the nonclassicality of the evolution of a superposition of an arbitrary number of photon-added squeezed coherent Schrödinger cat states in a nonlinear Kerr medium. The nonlinearity of the medium gives rise to the periodicities of the quantities such as the Wehrl entropy SQ and the negativity δW of the W-distribution, and a series of local minima of these quantities arise at the rational submultiples of the said period. At these local minima the evolving state coincides with the transient Yurke-Stoler type of photon-added squeezed kitten states, which, for the choice of the phase space variables reflecting their macroscopic nature, show extremely short-lived behavior. Proceeding further we provide the closed form tomograms, which furnish the alternate description of these short-lived states. The increasing complexity in the kitten formations induces more number of interference terms that trigger more quantumness of the corresponding states. The nonclassical depth of the photon-added squeezed kitten states are observed to be of maximum possible value. Employing the Lindblad master equation approach we study the amplitude and the phase damping models for the initial state considered here. In the phase damping model the nonclassicality is not completely erased even in the long time limit when the dynamical quantities, such as the negativity δW and the tomogram, assume nontrivial asymptotic values.

Human cerebral venous outflow pathway depends on posture and central venous pressure

DEFF Research Database (Denmark)

Gisolf, J; van Lieshout, J J; van Heusden, K

2004-01-01

Internal jugular veins are the major cerebral venous outflow pathway in supine humans. In upright humans the positioning of these veins above heart level causes them to collapse. An alternative cerebral outflow pathway is the vertebral venous plexus. We set out to determine the effect of posture...... and during a Valsalva manoeuvre in both body positions, correlate highly with model simulation of the jugular cross-sectional area (R(2) = 0.97). The results suggest that the cerebral venous flow distribution depends on posture and CVP: in supine humans the internal jugular veins are the primary pathway...

Control of neuropeptide expression by parallel activity-dependent pathways in caenorhabditis elegans

DEFF Research Database (Denmark)

Rojo Romanos, Teresa; Petersen, Jakob Gramstrup; Pocock, Roger

2017-01-01

Monitoring of neuronal activity within circuits facilitates integrated responses and rapid changes in behavior. We have identified a system in Caenorhabditis elegans where neuropeptide expression is dependent on the ability of the BAG neurons to sense carbon dioxide. In C. Elegans, CO 2 sensing...... is predominantly coordinated by the BAG-expressed receptor-type guanylate cyclase GCY-9. GCY-9 binding to CO 2 causes accumulation of cyclic GMP and opening of the cGMP-gated TAX-2/TAX-4 cation channels; provoking an integrated downstream cascade that enables C. Elegans to avoid high CO 2. Here we show that c...... that expression of flp-19::GFP is controlled in parallel to GCY-9 by the activity-dependent transcription factor CREB (CRH-1) and the cAMP-dependent protein kinase (KIN-2) signaling pathway. We therefore show that two parallel pathways regulate neuropeptide gene expression in the BAG sensory neurons: the ability...

The homology groups of moduli spaces on non-classical Klein surfaces

International Nuclear Information System (INIS)

Zaw, Myint

2001-08-01

We describe the moduli space M-vector±(g,c) of non-classical directed Klein surfaces of genus g=h-c-1 with c≥0 distinguished points as a configuration space B ± (h,c) of classes h-slit pairs in C. Based on this model, we prove that M-vector ± (g,c) is non-orientable for any g and c and we compute the homology groups of the moduli spaces M-vector ± (g,c) for g≤2. (author)

Nonclassical-light generation in a photonic-band-gap nonlinear planar waveguide

International Nuclear Information System (INIS)

Perina, Jan Jr.; Sibilia, Concita; Tricca, Daniela; Bertolotti, Mario

2004-01-01

The optical parametric process occurring in a photonic-band-gap planar waveguide is studied from the point of view of nonclassical-light generation. The nonlinearly interacting optical fields are described by the generalized superposition of coherent signals and noise using the method of operator linear corrections to a classical strong solution. Scattered backward-propagating fields are taken into account. Squeezed light as well as light with sub-Poissonian statistics can be obtained in two-mode fields under the specified conditions

RANS-based simulation of turbulent wave boundary layer and sheet-flow sediment transport processes

DEFF Research Database (Denmark)

Fuhrman, David R.; Schløer, Signe; Sterner, Johanna

2013-01-01

A numerical model coupling the horizontal component of the incompressible Reynolds-averaged Navier–Stokes (RANS) equationswith two-equation k−ω turbulence closure is presented and used to simulate a variety of turbulent wave boundary layer processes. The hydrodynamic model is additionally coupled...... with bed and suspended load descriptions, the latter based on an unsteady turbulent-diffusion equation, for simulation of sheet-flow sediment transport processes. In addition to standard features common within such RANS-based approaches, the present model includes: (1) hindered settling velocities at high...

The canonical Wnt signaling pathway promotes chondrocyte differentiation in a Sox9-dependent manner

International Nuclear Information System (INIS)

Yano, Fumiko; Kugimiya, Fumitaka; Ohba, Shinsuke; Ikeda, Toshiyuki; Chikuda, Hirotaka; Ogasawara, Toru; Ogata, Naoshi; Takato, Tsuyoshi; Nakamura, Kozo; Kawaguchi, Hiroshi; Chung, Ung-il

2005-01-01

To better understand the role of the canonical Wnt signaling pathway in cartilage development, we adenovirally expressed a constitutively active (Canada) or a dominant negative (dn) form of lymphoid enhancer factor-1 (LEF-1), the main nuclear effector of the pathway, in undifferentiated mesenchymal cells, chondrogenic cells, and primary chondrocytes, and examined the expression of markers for chondrogenic differentiation and hypertrophy. caLEF-1 and LiCl, an activator of the canonical pathway, promoted both chondrogenic differentiation and hypertrophy, whereas dnLEF-1 and the gene silencing of β-catenin suppressed LiCl-promoted effects. To investigate whether these effects were dependent on Sox9, a master regulator of cartilage development, we stimulated Sox9-deficient ES cells with the pathway. caLEF-1 and LiCl promoted both chondrogenic differentiation and hypertrophy in wild-type, but not in Sox9-deficient, cells. The response of Sox9-deficient cells was restored by the adenoviral expression of Sox9. Thus, the canonical Wnt signaling pathway promotes chondrocyte differentiation in a Sox9-dependent manner

RISET STRATEGI IMPLEMENTASI C-RAN DI TELKOMSEL MELALUI KOLABORASI JARINGAN NG-PON2 DI TELKOM AKSES MENGGUNAKAN PENDEKATAN METODE STRATEGIC SITUATION ANALYSIS

Directory of Open Access Journals (Sweden)

Tri Susanto

2007-07-01

Full Text Available Cloud Radio Access Network (C-RAN adalah teknologi akses radio yang diyakini mampu menekan biaya CAPEX dan OPEX dari mobile operator dan memberikan performansi yang lebih baik dibandingkan Radio Access Network (RAN tradisional. Salah satu faktor kunci sukses implementasi C-RAN adalah penyediaan jaringan fonthaul yang efektif. Tujuan penelitian ini adalah membuat strategi implementasi C-RAN di Telkomsel melalui kolaborasi jaringan NG-PON2 di Telkom Akses. Pada tulisan ini menggunakan metode analisis kualitatif dengan melakukan strategy situation analysis (SSA yaitu melakukan analisa data eksternal maupun internal dan selanjutnya diformulasikan sebagai dasar pembuatan strategi implementasi. Dari penelitian ini dihasilkan usulan strategi implementasi C-RAN di Telkomsel melalui kolaborasi jaringan NG-PON2 di Telkom Akses.

RANS based CFD methodology for a real scale 217-pin wire-wrapped fuel assembly of KAERI PGSFR

Energy Technology Data Exchange (ETDEWEB)

Jeong, Jae-Ho, E-mail: jhjeong@kaeri.re.kr [Korea Atomic Energy Research Institute, 989-111 Daedeok-daero, Yuseoung-gu, Daejeon (Korea, Republic of); Song, Min-Seop [Department of Nuclear Engineering, Seoul National University, 559 Gwanak-ro, Gwanak-gu, Seoul (Korea, Republic of); Lee, Kwi-Lim [Korea Atomic Energy Research Institute, 989-111 Daedeok-daero, Yuseoung-gu, Daejeon (Korea, Republic of)

2017-03-15

Highlights: • This paper presents a suitable way for a practical RANS based CFD methodology which is applicable to real scale 217-pin wire-wrapped fuel assembly of KAERI PGSFR. • A key point of differentiation of the RANS based CFD methodology in this study is adapting an innovative grid generation method using a fortran based in-house code with a GGI function in a general-purpose commercial CFD code, CFX. • The RANS based CFD methodology is implemented with high resolution scheme and SST turbulence model in the 7-pin 37-pin, and 127-pin wire-wrapped fuel assembly of PNC and JNC. Furthermore, the RANS based CFD methodology can be successfully extended to the real scale 217-pin wire-wrapped fuel bundles of KAERI PGSFR. • Three-dimensional thermal-hydraulic characteristics have been also investigated briefly. - Abstract: This paper presents a suitable way for a practical RANS (Reynolds Averaged Navier-Stokes simulation) based CFD (Computational Fluid Dynamics) methodology which is applicable to real scale 217-pin wire-wrapped fuel assembly of KAERI (Korea Atomic Energy Research Institute) PGSFR (Prototype Gen-IV Sodium-cooled Fast Reactor). The main purpose of the current study is to support license issue for the KAERI PGSFR core safety and to elucidate thermal-hydraulic characteristics in a 217-pin wire-wrapped fuel assembly of KAERI PGSFR. A key point of differentiation of the RANS based CFD methodology in this study is adapting an innovative grid generation method using a fortran based in-house code with a GGI (General Grid Interface) function in a general-purpose commercial CFD code, CFX. The innovative grid generation method with GGI function can achieve to simulate a real wire shape with minimizing cell skewness. The RANS based CFD methodology is implemented with high resolution scheme in convection term and SST (Shear Stress Transport) turbulence model in the 7-pin 37-pin, and 127-pin wire-wrapped fuel assembly of PNC (Power reactor and Nuclear fuel

A RANS knock model to predict the statistical occurrence of engine knock

International Nuclear Information System (INIS)

D'Adamo, Alessandro; Breda, Sebastiano; Fontanesi, Stefano; Irimescu, Adrian; Merola, Simona Silvia; Tornatore, Cinzia

2017-01-01

Highlights: • Development of a new RANS model for SI engine knock probability. • Turbulence-derived transport equations for variances of mixture fraction and enthalpy. • Gasoline autoignition delay times calculated from detailed chemical kinetics. • Knock probability validated against experiments on optically accessible GDI unit. • PDF-based knock model accounting for the random nature of SI engine knock in RANS simulations. - Abstract: In the recent past engine knock emerged as one of the main limiting aspects for the achievement of higher efficiency targets in modern spark-ignition (SI) engines. To attain these requirements, engine operating points must be moved as close as possible to the onset of abnormal combustions, although the turbulent nature of flow field and SI combustion leads to possibly ample fluctuations between consecutive engine cycles. This forces engine designers to distance the target condition from its theoretical optimum in order to prevent abnormal combustion, which can potentially damage engine components because of few individual heavy-knocking cycles. A statistically based RANS knock model is presented in this study, whose aim is the prediction not only of the ensemble average knock occurrence, poorly meaningful in such a stochastic event, but also of a knock probability. The model is based on look-up tables of autoignition times from detailed chemistry, coupled with transport equations for the variance of mixture fraction and enthalpy. The transported perturbations around the ensemble average value are based on variable gradients and on a local turbulent time scale. A multi-variate cell-based Gaussian-PDF model is proposed for the unburnt mixture, resulting in a statistical distribution for the in-cell reaction rate. An average knock precursor and its variance are independently calculated and transported; this results in the prediction of an earliest knock probability preceding the ensemble average knock onset, as confirmed by

"Nonclassical" secretion of annexin A2 to the lumenal side of the enterocyte brush border membrane

DEFF Research Database (Denmark)

Danielsen, E Michael; van Deurs, Bo; Hansen, Gert H

2003-01-01

side of the microvilli, showing an apical secretion by a "nonclassical" mechanism. In addition, annexin A2 was associated with surface-connected, deep apical tubules in the apical terminal web region and with an underlying pleiomorphic, tubulo-vesicular compartment (subapical compartment...

Integral Method for the Assessment of U-RANS Effectiveness in Non-Equilibrium Flows and Heat Transfer

Science.gov (United States)

Pond, Ian; Edabi, Alireza; Dubief, Yves; White, Christopher

2015-11-01

Reynolds Average Navier Stokes (RANS) modeling has established itself as a critical design tool in many engineering applications, thanks to its superior computational efficiency. The drawbacks of RANS models are well known, but not necessarily well understood: poor prediction of transition, non equilibrium flows, mixing and heat transfer, to name the ones relevant to our study. In the present study, we use a DNS of a reciprocating channel flow driven by an oscillating pressure gradient to test several low- and high-Reynolds RANS models. Temperature is introduced as a passive scalar to study heat transfer modeling. Low-Reynolds models manage to capture the overall physics of wall shear and heat flux well, yet with some phase discrepancies, whereas high Reynolds models fail. Under the microscope of the integral method for wall shear and wall heat flux, the qualitative agreement appears more serendipitous than driven by the ability of the models to capture the correct physics. The integral method is shown to be more insightful in the benchmarking of RANS models than the typical comparisons of statistical quantities. The authors acknowledges the support of NSF and DOE under grant NSF/DOE 1258697 (VT) and 1258702 (NH).

Non-classical state engineering for quantum networks

International Nuclear Information System (INIS)

Vollmer, Christina E.

2014-01-01

The wide field of quantum information processing and quantum networks has developed very fast in the last two decades. Besides the regime of discrete variables, which was developed first, the regime of continuous variables represents an alternative approach to realize many quantum applications. Non-classical states of light, like squeezed or entangled states, are a fundamental resource for quantum applications like quantum repeaters, quantum memories, quantum key distribution, quantum spectroscopy, and quantum metrology. These states can be generated successfully in the infrared wavelength regime. However, for some tasks other wavelengths, especially in the visible wavelength regime, are desirable. To generate non-classical states of light in this wavelength regime frequency up-conversion can be used, since all quantum properties are maintained in this process. The first part of this thesis deals with the experimental frequency up-conversion of quantum states. Squeezed vacuum states of light at 1550 nm were up-converted to 532 nm and a noise reduction of -1.5 dB at 532 nm was achieved. These states can be used for increasing the sensitivity of gravitational wave detectors or spectroscopic measurements. Furthermore, one part of an entangled state at 1550 nm was up-converted to 532 nm and, thus, entanglement between these two wavelengths was generated and characterized to -1.4 dB following Duan et al. With such a quantum link it is possible to establish a quantum network, which takes advantage of the low optical loss at 1550 nm for information transmission and of atomic transitions around 532 nm for a quantum memory in a quantum repeater. For quantum networks the distribution of entanglement and especially of a quantum key is essential. In the second part of this thesis the experimental distribution of entanglement by separable states is demonstrated. The underlying protocol requires a special three-mode state, which is separable in two of the three splittings. With

Non-classical state engineering for quantum networks

Energy Technology Data Exchange (ETDEWEB)

Vollmer, Christina E.

2014-01-24

The wide field of quantum information processing and quantum networks has developed very fast in the last two decades. Besides the regime of discrete variables, which was developed first, the regime of continuous variables represents an alternative approach to realize many quantum applications. Non-classical states of light, like squeezed or entangled states, are a fundamental resource for quantum applications like quantum repeaters, quantum memories, quantum key distribution, quantum spectroscopy, and quantum metrology. These states can be generated successfully in the infrared wavelength regime. However, for some tasks other wavelengths, especially in the visible wavelength regime, are desirable. To generate non-classical states of light in this wavelength regime frequency up-conversion can be used, since all quantum properties are maintained in this process. The first part of this thesis deals with the experimental frequency up-conversion of quantum states. Squeezed vacuum states of light at 1550 nm were up-converted to 532 nm and a noise reduction of -1.5 dB at 532 nm was achieved. These states can be used for increasing the sensitivity of gravitational wave detectors or spectroscopic measurements. Furthermore, one part of an entangled state at 1550 nm was up-converted to 532 nm and, thus, entanglement between these two wavelengths was generated and characterized to -1.4 dB following Duan et al. With such a quantum link it is possible to establish a quantum network, which takes advantage of the low optical loss at 1550 nm for information transmission and of atomic transitions around 532 nm for a quantum memory in a quantum repeater. For quantum networks the distribution of entanglement and especially of a quantum key is essential. In the second part of this thesis the experimental distribution of entanglement by separable states is demonstrated. The underlying protocol requires a special three-mode state, which is separable in two of the three splittings. With

Non-classical austenite-martensite interfaces observed in single crystals of Cu-Al-Ni

Czech Academy of Sciences Publication Activity Database

Seiner, Hanuš; Landa, Michal

2009-01-01

Roč. 82, č. 11 (2009), s. 793-807 ISSN 0141-1594 R&D Projects: GA AV ČR(CZ) IAA200100627; GA ČR(CZ) GP202/09/P164 Institutional research plan: CEZ:AV0Z20760514 Keywords : shape memory alloy s * martensitic microstructure * non-classical interfaces * crossing twins Subject RIV: BJ - Thermodynamics Impact factor: 0.935, year: 2009 http://www.informaworld.com

Mesh Generation and Adaption for High Reynolds Number RANS Computations, Phase I

Data.gov (United States)

National Aeronautics and Space Administration — This proposal offers to provide NASA with an automatic mesh generator for the simulation of aerodynamic flows using Reynolds-Averages Navier-Stokes (RANS) models....

Mesh Generation and Adaption for High Reynolds Number RANS Computations, Phase II

Data.gov (United States)

National Aeronautics and Space Administration — This proposal offers to provide NASA with an automatic mesh generator for the simulation of aerodynamic flows using Reynolds-Averages Navier-Stokes (RANS) models....

Quantum teleportation of nonclassical wave packets: An effective multimode theory

Energy Technology Data Exchange (ETDEWEB)

Benichi, Hugo; Takeda, Shuntaro; Lee, Noriyuki; Furusawa, Akira [Department of Applied Physics, University of Tokyo, Tokyo (Japan)

2011-07-15

We develop a simple and efficient theoretical model to understand the quantum properties of broadband continuous variable quantum teleportation. We show that, if stated properly, the problem of multimode teleportation can be simplified to teleportation of a single effective mode that describes the input state temporal characteristic. Using that model, we show how the finite bandwidth of squeezing and external noise in the classical channel affect the output teleported quantum field. We choose an approach that is especially relevant for the case of non-Gaussian nonclassical quantum states and we finally back-test our model with recent experimental results.

Non-classical solutions of a continuum model for rock descriptions

Directory of Open Access Journals (Sweden)

Mikhail A. Guzev

2014-06-01

Full Text Available The strain-gradient and non-Euclidean continuum theories are employed for construction of non-classical solutions of continuum models. The linear approximation of both models' results in identical structures in terms of their kinematic and stress characteristics. The solutions obtained in this study exhibit a critical behaviour with respect to the external loading parameter. The conclusions are obtained based on an investigation of the solution for the scalar curvature in the non-Euclidean continuum theory. The proposed analysis enables us to use different theoretical approaches for description of rock critical behaviour under different loading conditions.

Comparison of life cycle greenhouse gases from natural gas pathways for medium and heavy-duty vehicles.

Science.gov (United States)

Tong, Fan; Jaramillo, Paulina; Azevedo, Inês M L

2015-06-16

The low-cost and abundant supply of shale gas in the United States has increased the interest in using natural gas for transportation. We compare the life cycle greenhouse gas (GHG) emissions from different natural gas pathways for medium and heavy-duty vehicles (MHDVs). For Class 8 tractor-trailers and refuse trucks, none of the natural gas pathways provide emissions reductions per unit of freight-distance moved compared to diesel trucks. When compared to the petroleum-based fuels currently used in these vehicles, CNG and centrally produced LNG increase emissions by 0-3% and 2-13%, respectively, for Class 8 trucks. Battery electric vehicles (BEVs) powered with natural gas-produced electricity are the only fuel-technology combination that achieves emission reductions for Class 8 transit buses (31% reduction compared to the petroleum-fueled vehicles). For non-Class 8 trucks (pick-up trucks, parcel delivery trucks, and box trucks), BEVs reduce emissions significantly (31-40%) compared to their diesel or gasoline counterparts. CNG and propane achieve relatively smaller emissions reductions (0-6% and 19%, respectively, compared to the petroleum-based fuels), while other natural gas pathways increase emissions for non-Class 8 MHDVs. While using natural gas to fuel electric vehicles could achieve large emission reductions for medium-duty trucks, the results suggest there are no great opportunities to achieve large emission reductions for Class 8 trucks through natural gas pathways with current technologies. There are strategies to reduce the carbon footprint of using natural gas for MHDVs, ranging from increasing vehicle fuel efficiency, reducing life cycle methane leakage rate, to achieving the same payloads and cargo volumes as conventional diesel trucks.

Film thickness dependence of phase separation and dewetting behaviors in PMMA/SAN blend films.

Science.gov (United States)

You, Jichun; Liao, Yonggui; Men, Yongfeng; Shi, Tongfei; An, Lijia

2010-09-21

Film thickness dependence of complex behaviors coupled by phase separation and dewetting in blend [poly(methyl methacrylate) (PMMA) and poly(styrene-ran-acrylonitrile) (SAN)] films on silicon oxide substrate at 175 °C was investigated by grazing incidence ultrasmall-angle X-ray scattering (GIUSAX) and in situ atomic force microscopy (AFM). It was found that the dewetting pathway was under the control of the parameter U(q0)/E, which described the initial amplitude of the surface undulation and original thickness of film, respectively. Furthermore, our results showed that interplay between phase separation and dewetting depended crucially on film thickness. Three mechanisms including dewetting-phase separation/wetting, dewetting/wetting-phase separation, and phase separation/wetting-pseudodewetting were discussed in detail. In conclusion, it is relative rates of phase separation and dewetting that dominate the interplay between them.

A nuclear-receptor-dependent phosphatidylcholine pathway with antidiabetic effects.

Science.gov (United States)

Lee, Jae Man; Lee, Yoon Kwang; Mamrosh, Jennifer L; Busby, Scott A; Griffin, Patrick R; Pathak, Manish C; Ortlund, Eric A; Moore, David D

2011-05-25

Nuclear hormone receptors regulate diverse metabolic pathways and the orphan nuclear receptor LRH-1 (also known as NR5A2) regulates bile acid biosynthesis. Structural studies have identified phospholipids as potential LRH-1 ligands, but their functional relevance is unclear. Here we show that an unusual phosphatidylcholine species with two saturated 12 carbon fatty acid acyl side chains (dilauroyl phosphatidylcholine (DLPC)) is an LRH-1 agonist ligand in vitro. DLPC treatment induces bile acid biosynthetic enzymes in mouse liver, increases bile acid levels, and lowers hepatic triglycerides and serum glucose. DLPC treatment also decreases hepatic steatosis and improves glucose homeostasis in two mouse models of insulin resistance. Both the antidiabetic and lipotropic effects are lost in liver-specific Lrh-1 knockouts. These findings identify an LRH-1 dependent phosphatidylcholine signalling pathway that regulates bile acid metabolism and glucose homeostasis.

Extending the bounds of ‘steady’ RANS closures: Toward an instability-sensitive Reynolds stress model

International Nuclear Information System (INIS)

Jakirlić, S.; Maduta, R.

2015-01-01

Highlights: • A grid-spacing free, instability-sensitive Reynolds stress model is formulated. • The model is capable of capturing turbulence fluctuations. • Substantial improvement concerning proper turbulence activity enhancement is achieved. • The model is intensively validated in a series of 2D and 3D separating flows. • The model feasibility is also checked in some attached flows. - Abstract: The incapability of the conventional Unsteady RANS (Reynolds–Averaged Navier Stokes) models to adequately capture turbulence unsteadiness presents the prime motivation of the present work, which focuses on formulating an instability-sensitive, eddy-resolving turbulence model on the Second-Moment Closure level. The model scheme adopted, functioning as a ‘sub-scale’ model in the Unsteady RANS framework, represents a differential near-wall Reynolds stress model formulated in conjunction with the scale-supplying equation governing the homogeneous part of the inverse turbulent time scale ω h (ω h = ε h /k). The latter equation was straightforwardly obtained from the model equation describing the dynamics of the homogeneous part of the total viscous dissipation rate ε, defined as ε h = ε − 0.5ν∂ 2 k/(∂x j ∂x j ) (Jakirlic and Hanjalic, 2002), by applying the derivation rules to the expression for ω h . The model capability to account for vortex length and time scales variability was enabled through an additional term in the corresponding length-scale determining equation, providing a selective enhancement of its production, pertinent particularly to the highly unsteady separated shear layer region, modeled in terms of the von Karman length scale (comprising the second derivative of the velocity field) in line with the SAS (Scale-Adaptive Simulation) proposal (Menter and Egorov, 2010). The present model formulation, termed as SRANS model (Sensitized RANS), does not comprise any parameter depending explicitly on grid spacing. The predictive

An investigation into the reduction of log-layer mismatch in wall-modeled LES with a hybrid RANS/LES approach

Science.gov (United States)

Balin, Riccardo; Spalart, Philippe R.; Jansen, Kenneth E.

2017-11-01

Hybrid RANS/LES modeling approaches used in the context of wall-modeled LES (WMLES) of channel flows and boundary layers often suffer from a mismatch in the RANS and LES log-layer intercepts of the mean velocity profile. In the vicinity of the interface between the RANS and LES regions, the mean velocity gradient is too steep causing a departure from the log-law, an over-prediction of the velocity in the outer layer and an under-prediction of the skin-friction. This steep gradient is attributed to inadequate modeled Reynolds stresses in the upper portion of the RANS layer and at the interface. Channel flow computations were carried out with the IDDES approach of Shur et al. in WMLES mode based on the Spalart-Allmaras RANS model. This talk investigates the robustness of this approach for unstructured grids and explores changes required for grids where insufficient elevation of the Reynolds stresses is observed. Awards of computer time were provided by Innovative and Novel Computational Impact on Theory and Experiment (INCITE) and Early Science programs. Resources of the Argonne Leadership Computing Facility, a DOE Office of Science User Facility, were used.

Food Stamps and Food Insecurity: What Can Be Learned in the Presence of Nonclassical Measurement Error?

Science.gov (United States)

Gundersen, Craig; Kreider, Brent

2008-01-01

Policymakers have been puzzled to observe that food stamp households appear more likely to be food insecure than observationally similar eligible nonparticipating households. We reexamine this issue allowing for nonclassical reporting errors in food stamp participation and food insecurity. Extending the literature on partially identified…

Consequences of nonclassical measurement for the algorithmic description of continuous dynamical systems

Science.gov (United States)

Fields, Chris

1989-01-01

Continuous dynamical systems intuitively seem capable of more complex behavior than discrete systems. If analyzed in the framework of the traditional theory of computation, a continuous dynamical system with countablely many quasistable states has at least the computational power of a universal Turing machine. Such an analyses assumes, however, the classical notion of measurement. If measurement is viewed nonclassically, a continuous dynamical system cannot, even in principle, exhibit behavior that cannot be simulated by a universal Turing machine.

Francis-99 turbine numerical flow simulation of steady state operation using RANS and RANS/LES turbulence model

Science.gov (United States)

Minakov, A.; Platonov, D.; Sentyabov, A.; Gavrilov, A.

2017-01-01

We performed numerical simulation of flow in a laboratory model of a Francis hydroturbine at three regimes, using two eddy-viscosity- (EVM) and a Reynolds stress (RSM) RANS models (realizable k-ɛ, k-ω SST, LRR) and detached-eddy-simulations (DES), as well as large-eddy simulations (LES). Comparison of calculation results with the experimental data was carried out. Unlike the linear EVMs, the RSM, DES, and LES reproduced well the mean velocity components, and pressure pulsations in the diffusor draft tube. Despite relatively coarse meshes and insufficient resolution of the near-wall region, LES, DES also reproduced well the intrinsic flow unsteadiness and the dominant flow structures and the associated pressure pulsations in the draft tube.

Present state and future of CFD based on three-dimensional RANS analysis

International Nuclear Information System (INIS)

Kim, Kwang Yong

2004-01-01

Computational Fluid Dynamics (CFD) based on Navier-Stokes equations has been developed rapidly for several decades with the developments of high speed computers and numerical algorithms, and presently is regarded as an essential analysis tool in the engineering applications containing fluid flow and convective heat transfer. It is known that for turbulent flow the Navier-Stokes equations can be calculated precisely by Direct Numerical Simulation (DNS). However, DNS needs huge computing time even for simple low-Reynolds number flows, and thus is not practical. Large Eddy Simulation (LES) can be an alternative. But, LES also needs considerable computing time for the analysis of engineering flows, and have some problem in the methods. Therefore, the analysis methods using Reynolds-averaged Navier-stokes equations (RANS) and turbulence closure models are still regarded as the major techniques for the analysis of turbulent flows in spite of the inaccuracy of the prediction. In this presentation, the present state and the prospect of CFD based on three-dimensional RANS analysis are introduced for physical models and numerical algorithms with the engineering examples. Especially, for the analysis of two-phase flows in nuclear reactor, the recently developed techniques are also introduced. And, the presentation includes the methods of design optimization using RANS analysis and numerical optimization techniques with variety of the applications

Simulation of wing-body junction flows with hybrid RANS/LES methods

International Nuclear Information System (INIS)

Fu Song; Xiao Zhixiang; Chen Haixin; Zhang Yufei; Huang Jingbo

2007-01-01

In this paper, flows past two wing-body junctions, the Rood at zero angle of attack and NASA TN D-712 at 12.5 o angle of attack, are investigated with two Reynolds-Averaged Navier-Stokes (RANS) and large eddy simulation (LES) hybrid methods. One is detached eddy simulation (DES) and the other is delayed-DES, both are based on a weakly nonlinear two-equation k-ω model. While the RANS method can predict the mean flow behaviours reasonably accurately, its performance for the turbulent kinetic energy and shear stress, as compared with available experimental data, is not satisfactory. DES, through introducing a length scale in the dissipation terms of the turbulent kinetic energy equation, delivers flow separation, a vortex or the onset of vortex breakdown too early. DDES, with its delayed effect, shows a great improvement in flow structures and turbulence characteristics, and agrees well with measurements

An example of enhancement of a non-classical feature of a light beam by mixing with another classical light beam using a beam splitter

International Nuclear Information System (INIS)

Prakash, Hari; Mishra, Devendra Kumar

2005-01-01

We present here an example where a non-classical feature of a light beam is enhanced simply by mixing with another classical coherent light beam using a beam splitter. This non-classical feature is amplitude-squared squeezing of a Gaussian light beam expressed by a negative value of Y e or a negative value of the normalized quantity W e which can become more negative on enhancement. Here, these values comprise the density, annihilation and creation operators, respectively

Functional contribution of elevated circulating and hepatic non-classical CD14CD16 monocytes to inflammation and human liver fibrosis.

Directory of Open Access Journals (Sweden)

Henning W Zimmermann

Full Text Available BACKGROUND: Monocyte-derived macrophages critically perpetuate inflammatory responses after liver injury as a prerequisite for organ fibrosis. Experimental murine models identified an essential role for the CCR2-dependent infiltration of classical Gr1/Ly6C(+ monocytes in hepatic fibrosis. Moreover, the monocyte-related chemokine receptors CCR1 and CCR5 were recently recognized as important fibrosis modulators in mice. In humans, monocytes consist of classical CD14(+CD16(- and non-classical CD14(+CD16(+ cells. We aimed at investigating the relevance of monocyte subpopulations for human liver fibrosis, and hypothesized that 'non-classical' monocytes critically exert inflammatory as well as profibrogenic functions in patients during liver disease progression. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed circulating monocyte subsets from freshly drawn blood samples of 226 patients with chronic liver disease (CLD and 184 healthy controls by FACS analysis. Circulating monocytes were significantly expanded in CLD-patients compared to controls with a marked increase of the non-classical CD14(+CD16(+ subset that showed an activated phenotype in patients and correlated with proinflammatory cytokines and clinical progression. Correspondingly, CD14(+CD16(+ macrophages massively accumulated in fibrotic/cirrhotic livers, as evidenced by immunofluorescence and FACS. Ligands of monocyte-related chemokine receptors CCR2, CCR1 and CCR5 were expressed at higher levels in fibrotic and cirrhotic livers, while CCL3 and CCL4 were also systemically elevated in CLD-patients. Isolated monocyte/macrophage subpopulations were functionally characterized regarding cytokine/chemokine expression and interactions with primary human hepatic stellate cells (HSC in vitro. CD14(+CD16(+ monocytes released abundant proinflammatory cytokines. Furthermore, CD14(+CD16(+, but not CD14(+CD16(- monocytes could directly activate collagen-producing HSC. CONCLUSIONS/SIGNIFICANCE: Our data

GTPase Ran strongly accumulates at the kinetochores of somatic chromosomes in the spermatogonial mitoses of Acricotopus lucidus (Diptera, Chironomidae).

Science.gov (United States)

Staiber, Wolfgang

2014-07-01

Unequal chromosome segregation and spindle formation occurs in the last gonial mitosis in the germ line of the chironomid Acricotopus lucidus. During this differential mitosis, all germ line-limited chromosomes (=Ks) migrate undivided to only one pole of the cell, while the somatic chromosomes (=Ss) first remain in the metaphase plane, and with the arrival of the Ks at the pole, they then separate equally. The evolutionarily conserved GTPase Ran plays a crucial role in many cellular processes. This includes the regulation of microtubule nucleation and stabilisation at kinetochores and of spindle assembly during mitosis, which is promoted by a RanGTP concentration gradient that forms around the mitotic chromosomes (Kalab et al. in Science 295:2452-2456, 2002, Nature 440:697-701, 2006). In the present study, a strong accumulation of Ran was detected by immunofluorescence at the kinetochores of the Ss in normal gonial and differential gonial mitoses of males of A. lucidus. In contrast, no Ran accumulation was observed at the kinetochores of the Ss in the metaphases of brain ganglia mitoses or of aberrant spermatocytes or in metaphases I and II of spermatocyte meiotic divisions. Likewise, there was no accumulation at the kinetochores of Drosophila melanogaster mitotic chromosomes from larval brains. The specific accumulation of Ran at the kinetochores of the Ss in differential gonial mitoses of A. lucidus strongly suggests that Ran is involved in a mechanism acting in this exceptional mitosis, which retains the Ss at the metaphase plane and prevents a premature separation and unequal segregation of the Ss during monopolar migration of the Ks.

ON THE POLARIZATION OF CREATIVE CONSCIOUSNESS IN NON-CLASSICAL ERA OF RUSSIAN LITERATURE

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Oleg Nikolaevich Sklyarov

2014-10-01

Full Text Available The article deals with the phenomenon of "branch" of the total flow of philosophical and aesthetic quest in Russian postsimbolism in the early 20th century and the implications of this polarization in the literary process in the following decades. Special attention is paid to the specifics of the non-classical consciousness, an important feature of which is the intention of the "targeting" of artistic expression. The main lines of development of Russian literature in the 20th century are briefly described. The subject of primary attention of the author are mental peculiarities, features of creative thinking inherited in individuals of every from ideological and artistic "vectors", forming a common paradigm of national literature in the non-classical era. The understanding the specifics of the "middle" line of creative research, defined by the concept of "neotraditionalism" becomes the center of the problem field in the article. In understanding and presentation of the essence of the neotraditional type of creative consciousness author moves into the mainstream, a paved by work of V.I. Tyupa, who proposed in the early 90s as the term itself, taken now adopted by many scientists and methodological principles of neotraditionalism identification as a special type of mental orientation in art. 

Genome-Wide Gene Set Analysis for Identification of Pathways Associated with Alcohol Dependence

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Biernacka, Joanna M.; Geske, Jennifer; Jenkins, Gregory D.; Colby, Colin; Rider, David N.; Karpyak, Victor M.; Choi, Doo-Sup; Fridley, Brooke L.

2013-01-01

It is believed that multiple genetic variants with small individual effects contribute to the risk of alcohol dependence. Such polygenic effects are difficult to detect in genome-wide association studies that test for association of the phenotype with each single nucleotide polymorphism (SNP) individually. To overcome this challenge, gene set analysis (GSA) methods that jointly test for the effects of pre-defined groups of genes have been proposed. Rather than testing for association between the phenotype and individual SNPs, these analyses evaluate the global evidence of association with a set of related genes enabling the identification of cellular or molecular pathways or biological processes that play a role in development of the disease. It is hoped that by aggregating the evidence of association for all available SNPs in a group of related genes, these approaches will have enhanced power to detect genetic associations with complex traits. We performed GSA using data from a genome-wide study of 1165 alcohol dependent cases and 1379 controls from the Study of Addiction: Genetics and Environment (SAGE), for all 200 pathways listed in the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Results demonstrated a potential role of the “Synthesis and Degradation of Ketone Bodies” pathway. Our results also support the potential involvement of the “Neuroactive Ligand Receptor Interaction” pathway, which has previously been implicated in addictive disorders. These findings demonstrate the utility of GSA in the study of complex disease, and suggest specific directions for further research into the genetic architecture of alcohol dependence. PMID:22717047

Heat control in opto-mechanical system using quantum non-classicality

International Nuclear Information System (INIS)

Sharma, Sushamana; Senwar, Subash

2016-01-01

Cooling of matter to the quantum ground state is a primary directive of quantum control. In other words, to extract entropy from a quantum system, efficient indirect quantum measurements may be implemented. The main objective is the cooling of the oscillator either to its motional ground state or to non-classical states, such as low-number Fock states, squeezed states or entangled states. It is shown that the use of quantum control procedure is better choice for even experimental realizations because it leads to a squeezed steady state with less than one phonon on average. The steady state of system corresponds to cooling of the system.

Role of CSL-dependent and independent Notch signaling pathways in cell apoptosis.

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Zeng, Chong; Xing, Rui; Liu, Jing; Xing, Feiyue

2016-01-01

Apoptosis is a normally biological phenomenon in various organisms, involving complexly molecular mechanisms with a series of signaling processes. Notch signaling is found evolutionarily conserved in many species, playing a critical role in embryonic development, normal tissue homeostasis, angiogenesis and immunoregulation. The focus of this review is on currently novel advances about roles of CSL-dependent and independent Notch signaling pathways in cell apoptosis. The CSL can bind Notch intracellular domain (NIC) to act as a switch in mediating transcriptional activation or inactivation of the Notch signaling pathway downstream genes in the nucleus. It shows that CSL-dependent signaling regulates the cell apoptosis through Hes-1-PTEN-AKT-mTOR signaling, but rather the CSL-independent signaling mediates the cell apoptosis possibly via NIC-mTORC2-AKT-mTOR signaling, providing a new insight into apoptotic mechanisms.

Constraint-based modeling and kinetic analysis of the Smad dependent TGF-beta signaling pathway.

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Zhike Zi

Full Text Available BACKGROUND: Investigation of dynamics and regulation of the TGF-beta signaling pathway is central to the understanding of complex cellular processes such as growth, apoptosis, and differentiation. In this study, we aim at using systems biology approach to provide dynamic analysis on this pathway. METHODOLOGY/PRINCIPAL FINDINGS: We proposed a constraint-based modeling method to build a comprehensive mathematical model for the Smad dependent TGF-beta signaling pathway by fitting the experimental data and incorporating the qualitative constraints from the experimental analysis. The performance of the model generated by constraint-based modeling method is significantly improved compared to the model obtained by only fitting the quantitative data. The model agrees well with the experimental analysis of TGF-beta pathway, such as the time course of nuclear phosphorylated Smad, the subcellular location of Smad and signal response of Smad phosphorylation to different doses of TGF-beta. CONCLUSIONS/SIGNIFICANCE: The simulation results indicate that the signal response to TGF-beta is regulated by the balance between clathrin dependent endocytosis and non-clathrin mediated endocytosis. This model is useful to be built upon as new precise experimental data are emerging. The constraint-based modeling method can also be applied to quantitative modeling of other signaling pathways.

Highly Nonclassical Quantum States and Environment Induced Decoherence

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Foldi, Peter

2004-06-01

In this thesis concrete quantum systems are investigated in the framework of the environment induced decoherence. The focus is on the dynamics of highly nonclassical quantum states, the Wigner function of which are negative over some regions of their domains. One of the chosen physical systems is a diatomic molecule, where the potential energy of the nuclei is an anharmonic function of their distance. A system of two-level atoms, which can be important from the viewpoint of quantum information technology, is also investigated. A method is described that is valid in both systems and can determine the characteristic time of the decoherence in a dynamical way. The direction of the decoherence and its relation to energy dissipation is also studied. Finally, a scheme is proposed that can prepare decoherence-free states using the experimental techniques presently available.

DNS, LES and RANS of turbulent heat transfer in boundary layer with suddenly changing wall thermal conditions

International Nuclear Information System (INIS)

Hattori, Hirofumi; Yamada, Shohei; Tanaka, Masahiro; Houra, Tomoya; Nagano, Yasutaka

2013-01-01

Highlights: • We study the turbulent boundary layer with heat transfer by DNS. • Turbulent boundary layers with suddenly changing wall thermal conditions are observed. • The detailed turbulent statistics and structures in turbulent thermal boundary layer are discussed. • Turbulence models in LES and RANS are evaluated using DNS results. • LES and RANS are almost in good agreement with DNS results. -- Abstract: The objectives of this study are to investigate a thermal field in a turbulent boundary layer with suddenly changing wall thermal conditions by means of direct numerical simulation (DNS), and to evaluate predictions of a turbulence model in such a thermal field, in which DNS of spatially developing boundary layers with heat transfer can be conducted using the generation of turbulent inflow data as a method. In this study, two types of wall thermal condition are investigated using DNS and predicted by large eddy simulation (LES) and Reynolds-averaged Navier–Stokes equation simulation (RANS). In the first case, the velocity boundary layer only develops in the entrance of simulation, and the flat plate is heated from the halfway point, i.e., the adiabatic wall condition is adopted in the entrance, and the entrance region of thermal field in turbulence is simulated. Then, the thermal boundary layer develops along a constant temperature wall followed by adiabatic wall. In the second case, velocity and thermal boundary layers simultaneously develop, and the wall thermal condition is changed from a constant temperature to an adiabatic wall in the downstream region. DNS results clearly show the statistics and structure of turbulent heat transfer in a constant temperature wall followed by an adiabatic wall. In the first case, the entrance region of thermal field in turbulence can be also observed. Thus, both the development and the entrance regions in thermal fields can be explored, and the effects upstream of the thermal field on the adiabatic region are

Nonclassicality by Local Gaussian Unitary Operations for Gaussian States

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Yangyang Wang

2018-04-01

Full Text Available A measure of nonclassicality N in terms of local Gaussian unitary operations for bipartite Gaussian states is introduced. N is a faithful quantum correlation measure for Gaussian states as product states have no such correlation and every non product Gaussian state contains it. For any bipartite Gaussian state ρ A B , we always have 0 ≤ N ( ρ A B < 1 , where the upper bound 1 is sharp. An explicit formula of N for ( 1 + 1 -mode Gaussian states and an estimate of N for ( n + m -mode Gaussian states are presented. A criterion of entanglement is established in terms of this correlation. The quantum correlation N is also compared with entanglement, Gaussian discord and Gaussian geometric discord.

Assessment of brain activation regulation in first graders via RAN / RAS test

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Tatiana V. Akhutina

2015-03-01

Full Text Available RAN / RAS test (Rapid Automatized Naming / Rapid Alternating Stimulus has been used successfully used by many psychologists, primarily to predict the risk of dyslexia, as it includes a language component and requires good visual-verbal connections. However, The research demonstrates that the low speed of naming is an effective indicator of neurocognitive problems of information processing as a whole (learning difficulties in general, not just reading difficulties. This can be explained in two ways: disturbance of executive mental control and the difficulties of automatization: the difficulties of the transition from a controlled energy-consuming assignment to a less energy-consuming one. The second interpretation describes the problems of energy resources of cognitive functioning. It is similar to weak maintenance of cortical structures activation. However, using the test mentioned herewith for assessing functions of activation regulation has not been described previously. In terms of the Luria’s three functional units of the brain theory the RAN / RAS test can be considered as sensitive to the weakness of the first unit, whose function is to maintain the activity of cortical structures. So the aim of the research is to prove the possibility of assessing the activation regulation using the RAN / RAS test. This issue is relevant because neuropsychological tools for determining the weakness of Unit I functions are not quite sufficient, while the problem of “energetic” unit ranks first in the frequency of occurrence in children with learning disabilities.

A viral, transporter associated with antigen processing (TAP)-independent, high affinity ligand with alternative interactions endogenously presented by the nonclassical human leukocyte antigen E class I molecule.

Science.gov (United States)

Lorente, Elena; Infantes, Susana; Abia, David; Barnea, Eilon; Beer, Ilan; García, Ruth; Lasala, Fátima; Jiménez, Mercedes; Mir, Carmen; Morreale, Antonio; Admon, Arie; López, Daniel

2012-10-12

The transporter associated with antigen processing (TAP) enables the flow of viral peptides generated in the cytosol by the proteasome and other proteases to the endoplasmic reticulum, where they complex with nascent human leukocyte antigen (HLA) class I. Later, these peptide-HLA class I complexes can be recognized by CD8(+) lymphocytes. Cancerous cells and infected cells in which TAP is blocked, as well as individuals with unusable TAP complexes, are able to present peptides on HLA class I by generating them through TAP-independent processing pathways. Here, we identify a physiologically processed HLA-E ligand derived from the D8L protein in TAP-deficient vaccinia virus-infected cells. This natural high affinity HLA-E class I ligand uses alternative interactions to the anchor motifs previously described to be presented on nonclassical HLA class I molecules. This octameric peptide was also presented on HLA-Cw1 with similar binding affinity on both classical and nonclassical class I molecules. In addition, this viral peptide inhibits HLA-E-mediated cytolysis by natural killer cells. Comparison between the amino acid sequences of the presenting HLA-E and HLA-Cw1 alleles revealed a shared structural motif in both HLA class molecules, which could be related to their observed similar cross-reactivity affinities. This motif consists of several residues located on the floor of the peptide-binding site. These data expand the role of HLA-E as an antigen-presenting molecule.

The hedgehog pathway gene shifted functions together with the hmgcr-dependent isoprenoid biosynthetic pathway to orchestrate germ cell migration.

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Girish Deshpande

Full Text Available The Drosophila embryonic gonad is assembled from two distinct cell types, the Primordial Germ Cells (PGCs and the Somatic Gonadal Precursor cells (SGPs. The PGCs form at the posterior of blastoderm stage embryos and are subsequently carried inside the embryo during gastrulation. To reach the SGPs, the PGCs must traverse the midgut wall and then migrate through the mesoderm. A combination of local repulsive cues and attractive signals emanating from the SGPs guide migration. We have investigated the role of the hedgehog (hh pathway gene shifted (shf in directing PGC migration. shf encodes a secreted protein that facilitates the long distance transmission of Hh through the proteoglycan matrix after it is released from basolateral membranes of Hh expressing cells in the wing imaginal disc. shf is expressed in the gonadal mesoderm, and loss- and gain-of-function experiments demonstrate that it is required for PGC migration. Previous studies have established that the hmgcr-dependent isoprenoid biosynthetic pathway plays a pivotal role in generating the PGC attractant both by the SGPs and by other tissues when hmgcr is ectopically expressed. We show that production of this PGC attractant depends upon shf as well as a second hh pathway gene gγ1. Further linking the PGC attractant to Hh, we present evidence indicating that ectopic expression of hmgcr in the nervous system promotes the release/transmission of the Hh ligand from these cells into and through the underlying mesodermal cell layer, where Hh can contact migrating PGCs. Finally, potentiation of Hh by hmgcr appears to depend upon cholesterol modification.

Diosgenin induces apoptosis in IGF-1-stimulated human thyrocytes through two caspase-dependent pathways

International Nuclear Information System (INIS)

Mu, Shumin; Tian, Xingsong; Ruan, Yongwei; Liu, Yuantao; Bian, Dezhi; Ma, Chunyan; Yu, Chunxiao; Feng, Mei; Wang, Furong; Gao, Ling; Zhao, Jia-jun

2012-01-01

Highlights: ► Diosgenin induces apoptosis in IGF-1-treated thyrocytes through two caspase pathways. ► Diosgenin inhibits FLIP and activates caspase-8 in FAS related-pathway. ► Diosgenin increases ROS, regulates the ratio of Bax/Bcl-2 in mitochondrial pathway. -- Abstract: Insulin-like growth factor-1 (IGF-1) is a growth factor of the thyroid that has been shown in our previous study to possess proliferative and antiapoptotic effects in FRTL-5 cell lines through the upregulation of cyclin D and Fas-associated death domain-like interleukin-1-converting enzyme (FLICE)-inhibitory protein (FLIP). Diosgenin, a natural steroid sapogenin from plants, has been shown to induce apoptosis in many cell lines, with the exception of thyroid cells. In this report, we investigated the apoptotic effect and mechanism of diosgenin in IGF-1-stimulated primary human thyrocytes. Primary human thyrocytes were preincubated with or without IGF-1 for 24 h and subsequently exposed to varying concentrations of diosgenin for different times. We found that diosgenin induced apoptosis in human thyrocytes pretreated with IGF-1 in a dose-dependent manner through the activation of caspase cascades. Moreover, diosgenin inhibited FLIP and activated caspase-8 in the FAS-related apoptotic pathway. Diosgenin increased the production of ROS, regulated the balance of Bax and Bcl-2 and cleaved caspase-9 in the mitochondrial apoptotic pathway. These results indicate that diosgenin induces apoptosis in IGF-1-stimulated primary human thyrocytes through two caspase-dependent pathways.

RANS Modeling of Stably Stratified Turbulent Boundary Layer Flows in OpenFOAM®

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Wilson Jordan M.

2015-01-01

Full Text Available Quantifying mixing processes relating to the transport of heat, momentum, and scalar quantities of stably stratified turbulent geophysical flows remains a substantial task. In a stably stratified flow, such as the stable atmospheric boundary layer (SABL, buoyancy forces have a significant impact on the flow characteristics. This study investigates constant and stability-dependent turbulent Prandtl number (Prt formulations linking the turbulent viscosity (νt and diffusivity (κt for modeling applications of boundary layer flows. Numerical simulations of plane Couette flow and pressure-driven channel flow are performed using the Reynolds-averaged Navier-Stokes (RANS framework with the standard k-ε turbulence model. Results are compared with DNS data to evaluate model efficacy for predicting mean velocity and density fields. In channel flow simulations, a Prandtl number formulation for wall-bounded flows is introduced to alleviate overmixing of the mean density field. This research reveals that appropriate specification of Prt can improve predictions of stably stratified turbulent boundary layer flows.

Hepatitis C virus NS2 protein activates cellular cyclic AMP-dependent pathways

International Nuclear Information System (INIS)

Kim, Kyoung Mi; Kwon, Shi-Nae; Kang, Ju-Il; Lee, Song Hee; Jang, Sung Key; Ahn, Byung-Yoon; Kim, Yoon Ki

2007-01-01

Chronic infection of the hepatitis C virus (HCV) leads to liver cirrhosis and cancer. The mechanism leading to viral persistence and hepatocellular carcinoma, however, has not been fully understood. In this study, we show that the HCV infection activates cellular cAMP-dependent pathways. Expression of a luciferase reporter gene controlled by a basic promoter with the cAMP response element (CRE) was significantly elevated in human hepatoma Huh-7 cells infected with the HCV JFH1. Analysis with viral subgenomic replicons indicated that the HCV NS2 protein is responsible for the effect. Furthermore, the level of cellular transcripts whose stability is known to be regulated by cAMP was specifically reduced in cells harboring NS2-expressing replicons. These results allude to the HCV NS2 protein having a novel function of regulating cellular gene expression and proliferation through the cAMP-dependent pathway

Calcium-Dependent Protein Kinases in Phytohormone Signaling Pathways

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Wuwu Xu

2017-11-01

Full Text Available Calcium-dependent protein kinases (CPKs/CDPKs are Ca2+-sensors that decode Ca2+ signals into specific physiological responses. Research has reported that CDPKs constitute a large multigene family in various plant species, and play diverse roles in plant growth, development, and stress responses. Although numerous CDPKs have been exhaustively studied, and many of them have been found to be involved in plant hormone biosynthesis and response mechanisms, a comprehensive overview of the manner in which CDPKs participate in phytohormone signaling pathways, regulating nearly all aspects of plant growth, has not yet been undertaken. In this article, we reviewed the structure of CDPKs and the mechanism of their subcellular localization. Some CDPKs were elucidated to influence the intracellular localization of their substrates. Since little work has been done on the interaction between CDPKs and cytokinin signaling pathways, or on newly defined phytohormones such as brassinosteroids, strigolactones and salicylic acid, this paper mainly focused on discussing the integral associations between CDPKs and five plant hormones: auxins, gibberellins, ethylene, jasmonates, and abscisic acid. A perspective on future work is provided at the end.

Replacing Escherichia coli NAD-dependent glyceraldehyde 3-phosphate dehydrogenase (GAPDH) with a NADP-dependent enzyme from Clostridium acetobutylicum facilitates NADPH dependent pathways.

Science.gov (United States)

Martínez, Irene; Zhu, Jiangfeng; Lin, Henry; Bennett, George N; San, Ka-Yiu

2008-11-01

Reactions requiring reducing equivalents, NAD(P)H, are of enormous importance for the synthesis of industrially valuable compounds such as carotenoids, polymers, antibiotics and chiral alcohols among others. The use of whole-cell biocatalysis can reduce process cost by acting as catalyst and cofactor regenerator at the same time; however, product yields might be limited by cofactor availability within the cell. Thus, our study focussed on the genetic manipulation of a whole-cell system by modifying metabolic pathways and enzymes to improve the overall production process. In the present work, we genetically engineered an Escherichia coli strain to increase NADPH availability to improve the productivity of products that require NADPH in its biosynthesis. The approach involved an alteration of the glycolysis step where glyceraldehyde-3-phosphate (GAP) is oxidized to 1,3 bisphophoglycerate (1,3-BPG). This reaction is catalyzed by NAD-dependent endogenous glyceraldehyde-3-phosphate dehydrogenase (GAPDH) encoded by the gapA gene. We constructed a recombinant E. coli strain by replacing the native NAD-dependent gapA gene with a NADP-dependent GAPDH from Clostridium acetobutylicum, encoded by the gene gapC. The beauty of this approach is that the recombinant E. coli strain produces 2 mol of NADPH, instead of NADH, per mole of glucose consumed. Metabolic flux analysis showed that the flux through the pentose phosphate (PP) pathway, one of the main pathways that produce NADPH, was reduced significantly in the recombinant strain when compared to that of the parent strain. The effectiveness of the NADPH enhancing system was tested using the production of lycopene and epsilon-caprolactone as model systems using two different background strains. The recombinant strains, with increased NADPH availability, consistently showed significant higher productivity than the parent strains.

COPS5 (Jab1) protein increases β site processing of amyloid precursor protein and amyloid β peptide generation by stabilizing RanBP9 protein levels.

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Wang, Hongjie; Dey, Debleena; Carrera, Ivan; Minond, Dmitriy; Bianchi, Elisabetta; Xu, Shaohua; Lakshmana, Madepalli K

2013-09-13

Increased processing of amyloid precursor protein (APP) and accumulation of neurotoxic amyloid β peptide (Aβ) in the brain is central to the pathogenesis of Alzheimer's disease (AD). Therefore, the identification of molecules that regulate Aβ generation is crucial for future therapeutic approaches for AD. We demonstrated previously that RanBP9 regulates Aβ generation in a number of cell lines and primary neuronal cultures by forming tripartite protein complexes with APP, low-density lipoprotein-related protein, and BACE1, consequently leading to increased amyloid plaque burden in the brain. RanBP9 is a scaffold protein that exists and functions in multiprotein complexes. To identify other proteins that may bind RanBP9 and regulate Aβ levels, we used a two-hybrid analysis against a human brain cDNA library and identified COPS5 as a novel RanBP9-interacting protein. This interaction was confirmed by coimmunoprecipitation experiments in both neuronal and non-neuronal cells and mouse brain. Colocalization of COPS5 and RanBP9 in the same subcellular compartments further supported the interaction of both proteins. Furthermore, like RanBP9, COPS5 robustly increased Aβ generation, followed by increased soluble APP-β (sAPP-β) and decreased soluble-APP-α (sAPP-α) levels. Most importantly, down-regulation of COPS5 by siRNAs reduced Aβ generation, implying that endogenous COPS5 regulates Aβ generation. Finally, COPS5 levels were increased significantly in AD brains and APΔE9 transgenic mice, and overexpression of COPS5 strongly increased RanBP9 protein levels by increasing its half-life. Taken together, these results suggest that COPS5 increases Aβ generation by increasing RanBP9 levels. Thus, COPS5 is a novel RanBP9-binding protein that increases APP processing and Aβ generation by stabilizing RanBP9 protein levels.

Computing the flow past Vortex Generators : Comparison between RANS Simulations and Experiments

NARCIS (Netherlands)

Manolesos, M.; Sorensen, NN; Troldborg, N.; Florentie, L.; Papadakis, G; Voutsinas, S.

2016-01-01

The flow around a wind turbine airfoil equipped with Vortex Generators (VGs) is examined. Predictions from three different Reynolds Averaged Navier Stokes (RANS) solvers with two different turbulence models and two different VG modelling approaches are compared between them and with experimental

Benchmarking LES with wall-functions and RANS for fatigue problems in thermal–hydraulics systems

Energy Technology Data Exchange (ETDEWEB)

Tunstall, R., E-mail: ryan.tunstall@manchester.ac.uk [School of MACE, The University of Manchester, Manchester M13 9PL (United Kingdom); Laurence, D.; Prosser, R. [School of MACE, The University of Manchester, Manchester M13 9PL (United Kingdom); Skillen, A. [Scientific Computing Department, STFC Daresbury Laboratory, Warrington WA4 4AD (United Kingdom)

2016-11-15

Highlights: • We benchmark LES with blended wall-functions and low-Re RANS for a pipe bend and T-Junction. • Blended wall-laws allow the first cell from the wall to be placed anywhere in the boundary layer. • In both cases LES predictions improve as the first cell wall spacing is reduced. • Near-wall temperature fluctuations in the T-Junction are overpredicted by wall-modelled LES. • The EBRSM outperforms other RANS models for the pipe bend. - Abstract: In assessing whether nuclear plant components such as T-Junctions are likely to suffer thermal fatigue problems in service, CFD techniques need to provide accurate predictions for wall temperature fluctuations. Though it has been established that this is within the capabilities of wall-resolved LES, its high computational cost has prevented widespread usage in industry. In the present paper the suitability of LES with blended wall-functions, that allow the first cell to be placed in any part of the boundary layer, is assessed. Numerical results for the flows through a 90° pipe bend and a T-Junction are compared against experimental data. Both test cases contain areas where equilibrium laws are violated in practice. It is shown that reducing the first cell wall spacing improves agreement with experimental data by limiting the extent from the wall in which the solution is constrained to an equilibrium law. The LES with wall-function approach consistently overpredicts the near-wall temperature fluctuations in the T-Junction, suggesting that it can be considered as a conservative approach. We also benchmark a range of low-Re RANS models. EBRSM predictions for the 90° pipe bend are in significantly better agreement with experimental data than those from the other models. There are discrepancies from all RANS models in the case of the T-Junction.

New fundamental evidence of non-classical structure in the combination of natural concepts.

Science.gov (United States)

Aerts, D; Sozzo, S; Veloz, T

2016-01-13

We recently performed cognitive experiments on conjunctions and negations of two concepts with the aim of investigating the combination problem of concepts. Our experiments confirmed the deviations (conceptual vagueness, underextension, overextension etc.) from the rules of classical (fuzzy) logic and probability theory observed by several scholars in concept theory, while our data were successfully modelled in a quantum-theoretic framework developed by ourselves. In this paper, we isolate a new, very stable and systematic pattern of violation of classicality that occurs in concept combinations. In addition, the strength and regularity of this non-classical effect leads us to believe that it occurs at a more fundamental level than the deviations observed up to now. It is our opinion that we have identified a deep non-classical mechanism determining not only how concepts are combined but, rather, how they are formed. We show that this effect can be faithfully modelled in a two-sector Fock space structure, and that it can be exactly explained by assuming that human thought is the superposition of two processes, a 'logical reasoning', guided by 'logic', and a 'conceptual reasoning', guided by 'emergence', and that the latter generally prevails over the former. All these findings provide new fundamental support to our quantum-theoretic approach to human cognition. © 2015 The Author(s).

Numerical study comparing RANS and LES approaches on a circulation control airfoil

International Nuclear Information System (INIS)

Rumsey, Christopher L.; Nishino, Takafumi

2011-01-01

Highlights: → RANS compared with LES for circulation control airfoil. → RANS turbulence models need to account for streamline curvature. → RANS models yield higher lift than LES in spite of predicting similar jet separation. - Abstract: A numerical study over a nominally two-dimensional circulation control airfoil is performed using a large-eddy simulation code and two Reynolds-averaged Navier-Stokes codes. Different Coanda jet blowing conditions are investigated. In addition to investigating the influence of grid density, a comparison is made between incompressible and compressible flow solvers. The incompressible equations are found to yield negligible differences from the compressible equations up to at least a jet exit Mach number of 0.64. The effects of different turbulence models are also studied. Models that do not account for streamline curvature effects tend to predict jet separation from the Coanda surface too late, and can produce non-physical solutions at high blowing rates. Three different turbulence models that account for streamline curvature are compared with each other and with large eddy simulation solutions. All three models are found to predict the Coanda jet separation location reasonably well, but one of the models predicts specific flow field details near the Coanda surface prior to separation much better than the other two. All Reynolds-averaged Navier-Stokes computations produce higher circulation than large eddy simulation computations, with different stagnation point location and greater flow acceleration around the nose onto the upper surface. The precise reasons for the higher circulation are not clear, although it is not solely a function of predicting the jet separation location correctly.

Numerical study comparing RANS and LES approaches on a circulation control airfoil

Energy Technology Data Exchange (ETDEWEB)

Rumsey, Christopher L., E-mail: c.l.rumsey@nasa.gov [Computational AeroSciences Branch, NASA Langley Research Center, Hampton, VA 23681-2199 (United States); Nishino, Takafumi [Advanced Supercomputing Division, NASA Ames Research Center, Moffett Field, CA 94035-1000 (United States)

2011-10-15

Highlights: > RANS compared with LES for circulation control airfoil. > RANS turbulence models need to account for streamline curvature. > RANS models yield higher lift than LES in spite of predicting similar jet separation. - Abstract: A numerical study over a nominally two-dimensional circulation control airfoil is performed using a large-eddy simulation code and two Reynolds-averaged Navier-Stokes codes. Different Coanda jet blowing conditions are investigated. In addition to investigating the influence of grid density, a comparison is made between incompressible and compressible flow solvers. The incompressible equations are found to yield negligible differences from the compressible equations up to at least a jet exit Mach number of 0.64. The effects of different turbulence models are also studied. Models that do not account for streamline curvature effects tend to predict jet separation from the Coanda surface too late, and can produce non-physical solutions at high blowing rates. Three different turbulence models that account for streamline curvature are compared with each other and with large eddy simulation solutions. All three models are found to predict the Coanda jet separation location reasonably well, but one of the models predicts specific flow field details near the Coanda surface prior to separation much better than the other two. All Reynolds-averaged Navier-Stokes computations produce higher circulation than large eddy simulation computations, with different stagnation point location and greater flow acceleration around the nose onto the upper surface. The precise reasons for the higher circulation are not clear, although it is not solely a function of predicting the jet separation location correctly.

Propagation of nonclassical correlations across a quantum spin chain

Energy Technology Data Exchange (ETDEWEB)

Campbell, S. [Centre for Theoretical Atomic, Molecular and Optical Physics, School of Mathematics and Physics, Queen' s University, Belfast BT7 1NN, Northern Ireland (United Kingdom); Physics Department, University College Cork, Cork (Ireland); Quantum Systems Unit, Okinawa Institute of Science and Technology, Okinawa (Japan); Apollaro, T. J. G. [Dipartimento di Fisica e Astronomia, Universita di Firenze, Via G. Sansone 1, IT-50019 Sesto Fiorentino (Italy); Di Franco, C. [Physics Department, University College Cork, Cork, Republic of Ireland (Ireland); Banchi, L.; Cuccoli, A. [Dipartimento di Fisica e Astronomia, Universita di Firenze, Via G. Sansone 1, IT-50019 Sesto Fiorentino (Italy); INFN Sezione di Firenze, via G.Sansone 1, IT-50019 Sesto Fiorentino (Italy); Vaia, R. [Istituto dei Sistemi Complessi, Consiglio Nazionale delle Ricerche, via Madonna del Piano 10, IT-50019 Sesto Fiorentino (Italy); Plastina, F. [Dipartimento di Fisica, Universita della Calabria, IT-87036 Arcavacata di Rende (Italy); INFN Gruppo collegato di Cosenza, Universita della Calabria, IT-87036, Arcavacata di Rende (Italy); Paternostro, M. [Centre for Theoretical Atomic, Molecular and Optical Physics, School of Mathematics and Physics, Queen' s University, Belfast BT7 1NN, Northern Ireland (United Kingdom)

2011-11-15

We study the transport of quantum correlations across a chain of interacting spin-1/2 particles. As a quantitative figure of merit, we choose a symmetric version of quantum discord and compare it with the transported entanglement, addressing various operating regimes of the spin medium. Discord turns out to be better transported for a wide range of working points and initial conditions of the system. We relate this behavior to the efficiency of propagation of a single excitation across the spin chain. Moreover, we point out the role played by a magnetic field in the dynamics of discord in the effective channel embodied by the chain. Our analysis can be interestingly extended to transport processes in more complex networks and the study of nonclassical correlations under general quantum channels.

Development of a Hybrid RANS/LES Method for Turbulent Mixing Layers

Science.gov (United States)

Georgiadis, Nicholas J.; Alexander, J. Iwan D.; Reshotko, Eli

2001-01-01

Significant research has been underway for several years in NASA Glenn Research Center's nozzle branch to develop advanced computational methods for simulating turbulent flows in exhaust nozzles. The primary efforts of this research have concentrated on improving our ability to calculate the turbulent mixing layers that dominate flows both in the exhaust systems of modern-day aircraft and in those of hypersonic vehicles under development. As part of these efforts, a hybrid numerical method was recently developed to simulate such turbulent mixing layers. The method developed here is intended for configurations in which a dominant structural feature provides an unsteady mechanism to drive the turbulent development in the mixing layer. Interest in Large Eddy Simulation (LES) methods have increased in recent years, but applying an LES method to calculate the wide range of turbulent scales from small eddies in the wall-bounded regions to large eddies in the mixing region is not yet possible with current computers. As a result, the hybrid method developed here uses a Reynolds-averaged Navier-Stokes (RANS) procedure to calculate wall-bounded regions entering a mixing section and uses a LES procedure to calculate the mixing-dominated regions. A numerical technique was developed to enable the use of the hybrid RANS-LES method on stretched, non-Cartesian grids. With this technique, closure for the RANS equations is obtained by using the Cebeci-Smith algebraic turbulence model in conjunction with the wall-function approach of Ota and Goldberg. The LES equations are closed using the Smagorinsky subgrid scale model. Although the function of the Cebeci-Smith model to replace all of the turbulent stresses is quite different from that of the Smagorinsky subgrid model, which only replaces the small subgrid turbulent stresses, both are eddy viscosity models and both are derived at least in part from mixing-length theory. The similar formulation of these two models enables the RANS

Diosgenin induces apoptosis in IGF-1-stimulated human thyrocytes through two caspase-dependent pathways

Energy Technology Data Exchange (ETDEWEB)

Mu, Shumin [Provincial Hospital Affiliated to Shandong University, Jinan 250021 (China); Hospital Affiliated to Shandong Traditional Chinese Medicine University, Jinan 250011 (China); Institute of Endocrinology, Shandong Academy of Clinical Medicine, Jinan 250021 (China); Tian, Xingsong; Ruan, Yongwei [Provincial Hospital Affiliated to Shandong University, Jinan 250021 (China); Liu, Yuantao [The Second Hospital of Shandong University, Jinan 250033 (China); Bian, Dezhi [Provincial Hospital Affiliated to Shandong University, Jinan 250021 (China); Jining Medical College, Jining 272013 (China); Ma, Chunyan [Provincial Hospital Affiliated to Shandong University, Jinan 250021 (China); Yu, Chunxiao [Provincial Hospital Affiliated to Shandong University, Jinan 250021 (China); Institute of Endocrinology, Shandong Academy of Clinical Medicine, Jinan 250021 (China); Feng, Mei [Provincial Hospital Affiliated to Shandong University, Jinan 250021 (China); Wang, Furong [Shandong University of Traditional Chinese Medicine, Jinan 250011 (China); Gao, Ling [Provincial Hospital Affiliated to Shandong University, Jinan 250021 (China); Institute of Endocrinology, Shandong Academy of Clinical Medicine, Jinan 250021 (China); Zhao, Jia-jun, E-mail: jjzhao@medmail.com.cn [Provincial Hospital Affiliated to Shandong University, Jinan 250021 (China); Institute of Endocrinology, Shandong Academy of Clinical Medicine, Jinan 250021 (China)

2012-02-10

Highlights: Black-Right-Pointing-Pointer Diosgenin induces apoptosis in IGF-1-treated thyrocytes through two caspase pathways. Black-Right-Pointing-Pointer Diosgenin inhibits FLIP and activates caspase-8 in FAS related-pathway. Black-Right-Pointing-Pointer Diosgenin increases ROS, regulates the ratio of Bax/Bcl-2 in mitochondrial pathway. -- Abstract: Insulin-like growth factor-1 (IGF-1) is a growth factor of the thyroid that has been shown in our previous study to possess proliferative and antiapoptotic effects in FRTL-5 cell lines through the upregulation of cyclin D and Fas-associated death domain-like interleukin-1-converting enzyme (FLICE)-inhibitory protein (FLIP). Diosgenin, a natural steroid sapogenin from plants, has been shown to induce apoptosis in many cell lines, with the exception of thyroid cells. In this report, we investigated the apoptotic effect and mechanism of diosgenin in IGF-1-stimulated primary human thyrocytes. Primary human thyrocytes were preincubated with or without IGF-1 for 24 h and subsequently exposed to varying concentrations of diosgenin for different times. We found that diosgenin induced apoptosis in human thyrocytes pretreated with IGF-1 in a dose-dependent manner through the activation of caspase cascades. Moreover, diosgenin inhibited FLIP and activated caspase-8 in the FAS-related apoptotic pathway. Diosgenin increased the production of ROS, regulated the balance of Bax and Bcl-2 and cleaved caspase-9 in the mitochondrial apoptotic pathway. These results indicate that diosgenin induces apoptosis in IGF-1-stimulated primary human thyrocytes through two caspase-dependent pathways.

Eulerian–Lagrangian RANS Model Simulations of the NIST Turbulent Methanol Spray Flame

NARCIS (Netherlands)

Zhu, Shanglong; Roekaerts, Dirk; Pozarlik, Artur Krzysztof; van der Meer, Theodorus H.

2015-01-01

A methanol spray flame in a combustion chamber of the NIST was simulated using an Eulerian–Lagrangian RANS model. Experimental data and previous numerical investigations by other researchers on this flame were analyzed to develop methods for more comprehensive model validation. The inlet boundary

Developmental pathways from child maltreatment to adolescent marijuana dependence: Examining moderation by FK506 binding protein 5 gene (FKBP5).

Science.gov (United States)

Handley, Elizabeth D; Rogosch, Fred A; Cicchetti, Dante

2015-11-01

The current study examined the prospective association between child maltreatment and the development of substance use disorder in adolescence with the aim of investigating pathways underlying this relation, as well as genetic moderation of these developmental mechanisms. Specifically, we tested whether youth who experienced maltreatment prior to age 8 were at risk for the development of marijuana dependence in adolescence by way of a childhood externalizing pathway and a childhood internalizing pathway. Moreover, we tested whether variation in FK506 binding protein 5 gene (FKBP5) CATT haplotype moderated these pathways. The participants were 326 children (n =179 maltreated; n = 147 nonmaltreated) assessed across two waves of data collection (childhood: ages 7-9 and adolescence: ages 15-18). Results indicated that higher levels of child externalizing symptoms significantly mediated the effect of child maltreatment on adolescent marijuana dependence symptoms for individuals with one or two copies of the FKBP5 CATT haplotype only. We did not find support for an internalizing pathway from child maltreatment to adolescent marijuana dependence, nor did we find evidence of moderation of the internalizing pathway by FKBP5 haplotype variation. Findings extend previous research by demonstrating that whether a maltreated child will traverse an externalizing pathway toward substance use disorder in adolescence is dependent on FKBP5 genetic variation.

Non-Classical C–H···X Hydrogen Bonding and Its Role in Asymmetric Organocatalysis

KAUST Repository

Ajitha, Manjaly John

2016-08-17

Non-classical hydrogen bonds (NCHBs) have attracted significant interest in the past decade particularly because of their important role in asymmetric catalytic systems. These weak interactions (< 4 kcal/mol) offer much flexibility in the preorganization of molecular entities required to achieve high enantioselectivity. Herein, we review some recent important organocatalytic asymmetric reactions where a NCHB serves as a critical factor in determining the stereoselectivity.

Critical role of RanBP2-mediated SUMOylation of Small Heterodimer Partner in maintaining bile acid homeostasis

Science.gov (United States)

Kim, Dong-Hyun; Kwon, Sanghoon; Byun, Sangwon; Xiao, Zhen; Park, Sean; Wu, Shwu-Yuan; Chiang, Cheng-Ming; Kemper, Byron; Kemper, Jongsook Kim

2016-01-01

Bile acids (BAs) are recently recognized signalling molecules that profoundly affect metabolism. Because of detergent-like toxicity, BA levels must be tightly regulated. An orphan nuclear receptor, Small Heterodimer Partner (SHP), plays a key role in this regulation, but how SHP senses the BA signal for feedback transcriptional responses is not clearly understood. We show an unexpected function of a nucleoporin, RanBP2, in maintaining BA homoeostasis through SUMOylation of SHP. Upon BA signalling, RanBP2 co-localizes with SHP at the nuclear envelope region and mediates SUMO2 modification at K68, which facilitates nuclear transport of SHP and its interaction with repressive histone modifiers to inhibit BA synthetic genes. Mice expressing a SUMO-defective K68R SHP mutant have increased liver BA levels, and upon BA- or drug-induced biliary insults, these mice exhibit exacerbated cholestatic pathologies. These results demonstrate a function of RanBP2-mediated SUMOylation of SHP in maintaining BA homoeostasis and protecting from the BA hepatotoxicity. PMID:27412403

Nonclassical Congenital Adrenal Hyperplasia and Pregnancy

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Neslihan Cuhaci

2015-01-01

Full Text Available Objective. The most common form of congenital adrenal hyperplasia (CAH is 21-hydroxylase (21-OH deficiency due to mutation of the CYP21A2 gene. Patients with nonclassical CAH (NC-CAH are usually asymptomatic at birth and typically present in late childhood, adolescence, or adulthood with symptoms of excessive androgen secretion. Subfertility is relative in NC-CAH, but the incidence of spontaneous miscarriage is higher. Here, we report a previously undiagnosed female who gave birth to a normal male child and is planning to become pregnant again. Case Report. A 32-year-old female was referred to our clinic for obesity. Her medical history revealed that she had had three pregnancies. She was planning to become pregnant again. Her laboratory results revealed that she had NC-CAH. Since her husband is the son of her aunt and she had miscarriages and intrauterin exitus in her history, their genetic analyses were performed. Conclusion. Since most patients with NC-CAH have a severe mutation, these patients may give birth to a child with the classical CAH (C-CAH if their partner is also carrying a severe mutation. Females with NC-CAH who desire pregnancy must be aware of the risk of having an infant with C-CAH.

Polydopamine-Functionalized CA-(PCL-ran-PLA) Nanoparticles for Target Delivery of Docetaxel and Chemo-photothermal Therapy of Breast Cancer

Science.gov (United States)

Kong, Na; Deng, Mei; Sun, Xiu-Na; Chen, Yi-Ding; Sui, Xin-Bing

2018-01-01

Current limitations of cancer therapy include the lack of effective strategy for target delivery of chemotherapeutic drugs, and the difficulty of achieving significant efficacy by single treatment. Herein, we reported a synergistic chemo-photothermal strategy based on aptamer (Apt)-polydopamine (pD) functionalized CA-(PCL-ran-PLA) nanoparticles (NPs) for effective delivery of docetaxel (DTX) and enhanced therapeutic effect. The developed DTX-loaded Apt-pD-CA-(PCL-ran-PLA) NPs achieved promising advantages, such as (i) improved drug loading content (LC) and encapsulation efficiency (EE) initiated by star-shaped copolymer CA-(PCL-ran-PLA); (ii) effective target delivery of drugs to tumor sites by incorporating AS1411 aptamers; (iii) significant therapeutic efficacy caused by synergistic chemo-photothermal treatment. In addition, the pD coating strategy with simple procedures could address the contradiction between targeting modification and maintaining formerly excellent bio-properties. Therefore, with excellent bio-properties and simple preparation procedures, the DTX-loaded Apt-pD-CA-(PCL-ran-PLA) NPs effectively increased the local drug concentration in tumor sites, minimized side effects, and significantly eliminated tumors, indicating the promising application of these NPs for cancer therapy. PMID:29527167

Humidity-dependent compression-induced glass transition of the air-water interfacial Langmuir films of poly(D,L-lactic acid-ran-glycolic acid) (PLGA).

Science.gov (United States)

Kim, Hyun Chang; Lee, Hoyoung; Jung, Hyunjung; Choi, Yun Hwa; Meron, Mati; Lin, Binhua; Bang, Joona; Won, You-Yeon

2015-07-28

Constant rate compression isotherms of the air-water interfacial Langmuir films of poly(D,L-lactic acid-ran-glycolic acid) (PLGA) show a distinct feature of an exponential increase in surface pressure in the high surface polymer concentration regime. We have previously demonstrated that this abrupt increase in surface pressure is linked to the glass transition of the polymer film, but the detailed mechanism of this process is not fully understood. In order to obtain a molecular-level understanding of this behavior, we performed extensive characterizations of the surface mechanical, structural and rheological properties of Langmuir PLGA films at the air-water interface, using combined experimental techniques including the Langmuir film balance, X-ray reflectivity and double-wall-ring interfacial rheometry methods. We observed that the mechanical and structural responses of the Langmuir PLGA films are significantly dependent on the rate of film compression; the glass transition was induced in the PLGA film only at fast compression rates. Surprisingly, we found that this deformation rate dependence is also dependent on the humidity of the environment. With water acting as a plasticizer for the PLGA material, the diffusion of water molecules through the PLGA film seems to be the key factor in the determination of the glass transformation properties and thus the mechanical response of the PLGA film against lateral compression. Based on our combined results, we hypothesize the following mechanism for the compression-induced glass transformation of the Langmuir PLGA film; (1) initially, a humidified/non-glassy PLGA film is formed in the full surface-coverage region (where the surface pressure shows a plateau) during compression; (2) further compression leads to the collapse of the PLGA chains and the formation of new surfaces on the air side of the film, and this newly formed top layer of the PLGA film is transiently glassy in character because the water evaporation rate

Intracellular calcium levels can regulate Importin-dependent nuclear import

International Nuclear Information System (INIS)

Kaur, Gurpreet; Ly-Huynh, Jennifer D.; Jans, David A.

2014-01-01

Highlights: • High intracellular calcium inhibits Impα/β1- or Impβ1-dependent nuclear protein import. • The effect of Ca 2+ on nuclear import does not relate to changes in the nuclear pore. • High intracellular calcium can result in mislocalisation of Impβ1, Ran and RCC1. - Abstract: We previously showed that increased intracellular calcium can modulate Importin (Imp)β1-dependent nuclear import of SRY-related chromatin remodeling proteins. Here we extend this work to show for the first time that high intracellular calcium inhibits Impα/β1- or Impβ1-dependent nuclear protein import generally. The basis of this relates to the mislocalisation of the transport factors Impβ1 and Ran, which show significantly higher nuclear localization in contrast to various other factors, and RCC1, which shows altered subnuclear localisation. The results here establish for the first time that intracellular calcium modulates conventional nuclear import through direct effects on the nuclear transport machinery

Intracellular calcium levels can regulate Importin-dependent nuclear import

Energy Technology Data Exchange (ETDEWEB)

Kaur, Gurpreet; Ly-Huynh, Jennifer D.; Jans, David A., E-mail: David.Jans@monash.edu

2014-07-18

Highlights: • High intracellular calcium inhibits Impα/β1- or Impβ1-dependent nuclear protein import. • The effect of Ca{sup 2+} on nuclear import does not relate to changes in the nuclear pore. • High intracellular calcium can result in mislocalisation of Impβ1, Ran and RCC1. - Abstract: We previously showed that increased intracellular calcium can modulate Importin (Imp)β1-dependent nuclear import of SRY-related chromatin remodeling proteins. Here we extend this work to show for the first time that high intracellular calcium inhibits Impα/β1- or Impβ1-dependent nuclear protein import generally. The basis of this relates to the mislocalisation of the transport factors Impβ1 and Ran, which show significantly higher nuclear localization in contrast to various other factors, and RCC1, which shows altered subnuclear localisation. The results here establish for the first time that intracellular calcium modulates conventional nuclear import through direct effects on the nuclear transport machinery.

IRAK2 directs stimulus-dependent nuclear export of inflammatory mRNAs.

Science.gov (United States)

Zhou, Hao; Bulek, Katarzyna; Li, Xiao; Herjan, Tomasz; Yu, Minjia; Qian, Wen; Wang, Han; Zhou, Gao; Chen, Xing; Yang, Hui; Hong, Lingzi; Zhao, Junjie; Qin, Luke; Fukuda, Koichi; Flotho, Annette; Gao, Ji; Dongre, Ashok; Carman, Julie A; Kang, Zizhen; Su, Bing; Kern, Timothy S; Smith, Jonathan D; Hamilton, Thomas A; Melchior, Frauke; Fox, Paul L; Li, Xiaoxia

2017-10-09

Expression of inflammatory genes is determined in part by post-transcriptional regulation of mRNA metabolism but how stimulus- and transcript-dependent nuclear export influence is poorly understood. Here, we report a novel pathway in which LPS/TLR4 engagement promotes nuclear localization of IRAK2 to facilitate nuclear export of a specific subset of inflammation-related mRNAs for translation in murine macrophages. IRAK2 kinase activity is required for LPS-induced RanBP2-mediated IRAK2 sumoylation and subsequent nuclear translocation. Array analysis showed that an SRSF1-binding motif is enriched in mRNAs dependent on IRAK2 for nuclear export. Nuclear IRAK2 phosphorylates SRSF1 to reduce its binding to target mRNAs, which promotes the RNA binding of the nuclear export adaptor ALYREF and nuclear export receptor Nxf1 loading for the export of the mRNAs. In summary, LPS activates a nuclear function of IRAK2 that facilitates the assembly of nuclear export machinery to export selected inflammatory mRNAs to the cytoplasm for translation.

Roux-en-Y gastric bypass in the treatment of non-classic congenital adrenal hyperplasia due to 11-hydroxylase deficiency.

Science.gov (United States)

Kalani, Amir; Thomas, Nithin; Sacerdote, Alan; Bahtiyar, Gül

2013-03-18

Non-classic adrenal hyperplasia (NCAH) has been associated with insulin resistance (IR). Therapies such as metformin, thiazolidinediones and lifestyle alterations improve IR and also ameliorate the biochemical and clinical abnormalities of NCAH, much as they do in polycystic ovarian syndrome (PCOS). More recently, bariatric surgery, such as Roux-en-Y gastric bypass (RYGBP), has also been associated with improvement in IR and amelioration of PCOS and may, therefore, be beneficial in NCAH. We report a case of a 39-year-old, deaf-mute, obese woman with NCAH due to 11-hydroxylase deficiency who underwent RYGBP followed by improvement of NCAH manifestations. She was initially treated with metformin and pioglitazone, which lowered serum 11-deoxycortisol from 198 ng/dl (irregular menses normalised as well. We conclude that RYGBP, like other interventions that reduce IR, may be another way of treating non-classic 11-hydroxylase deficiency in selected patients.

Ivan Rančić: A forgotten painter of flowers and landscapes

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Marković Kamenko M.

2014-01-01

Full Text Available Ivan Rančić was born in the Kraljevo village, in eastern Serbia to a family of farmers on 19th, February, 1906. Very little data about him has been preserved, therefore, this paper is an attempt to make a reconstruction of his life and work. He attended primary school in his birth place, lower secondary school he finished in Knjazevac and Military Academy in Belgrade. After completing the National Academy in 1934, he was sent to Zagreb where he got his first post. He lived there with his wife and his son until the capitulation of the country in 1941. A few months after the collapse of the country, he was arrested and sent to Ljubljana and three months later to a concentration camp in Austria. He spent about fifteen months in that camp in during which time he intensively studied painting. He fled from the camp to Switzerland and stayed there until his death in 1987. According to some letters he sent to his wife in Nis, some of his paintings he created during his time in the camp, ne took to Switzerland where he eventually sold them. He did the toughest jobs there in order to survive and painted extensively. After World War II he graduated from the School of Fine Arts in Lausanne. Later on he had two exhibitions at the New Gallery of Modern Art. Ivan Rančić came a long way from an unknown beginner to a respected prominent artist. He left behind about 350 works, many of which he sold during his life, mainly landscapes and still life in oil, watercolor and pastel. He was neither concerned about styles and trends nor did he believe in the old and the new. If he came to a certain specific manner of painting, it is because at one point it was imposed on him as the only proper way of expression. The analysis of Rančić's paintings leads to the conclusion that his creation had gone through four phases. The first one (started in the concentration camp in Austria during which he painted still lifes without full sketches, previous studies, and the use

A lentiviral sponge for miR-101 regulates RanBP9 expression and amyloid precursor protein metabolism in hippocampal neurons

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Christian eBarbato

2014-02-01

Full Text Available Neurodegeneration associated with amyloid β (Aβ peptide accumulation, synaptic loss, and memory impairment are pathophysiological features of Alzheimer's disease (AD. Numerous microRNAs regulate amyloid precursor protein (APP expression and metabolism. We previously reported that miR-101 is a negative regulator of APP expression in cultured hippocampal neurons. In this study, a search for predicted APP metabolism-associated miR-101 targets led to the identification of a conserved miR-101 binding site within the 3’ untranslated region (UTR of the mRNA encoding Ran-binding protein 9 (RanBP9. RanBP9 increases APP processing by β-amyloid converting enzyme 1 (BACE1, secretion of soluble APPβ (sAPPβ, and generation of Aβ. MiR-101 significantly reduced reporter gene expression when co-transfected with a RanBP9 3'-UTR reporter construct, while site-directed mutagenesis of the predicted miR-101 target site eliminated the reporter response. To investigate the effect of stable inhibition of miR-101 both in vitro and in vivo, a microRNA sponge was developed to bind miR-101 and derepress its targets. Four tandem bulged miR-101 responsive elements (REs, located downstream of the enhanced green fluorescence protein (EGFP open reading frame and driven by the synapsin promoter, were placed in a lentiviral vector to create the pLSyn-miR-101 sponge. Delivery of the sponge to primary hippocampal neurons significantly increased both APP and RanBP9 expression, as well as sAPPβ levels in the conditioned medium. Importantly, silencing of endogenous RanBP9 reduced sAPPβ levels in miR-101 sponge-containing hippocampal cultures, indicating that miR-101 inhibition may increase amyloidogenic processing of APP by RanBP9. Lastly, the impact of miR-101 on its targets was demonstrated in vivo by intrahippocampal injection of the pLSyn-miR-101 sponge into C57BL6 mice. This study thus provides the basis for studying the consequences of long-term miR-101 inhibition on

Succinate modulates Ca(2+) transient and cardiomyocyte viability through PKA-dependent pathway.

Science.gov (United States)

Aguiar, Carla J; Andrade, Vanessa L; Gomes, Enéas R M; Alves, Márcia N M; Ladeira, Marina S; Pinheiro, Ana Cristina N; Gomes, Dawidson A; Almeida, Alvair P; Goes, Alfredo M; Resende, Rodrigo R; Guatimosim, Silvia; Leite, M Fatima

2010-01-01

GPR91 is an orphan G-protein-coupled receptor (GPCR) that has been characterized as a receptor for succinate, a citric acid cycle intermediate, in several tissues. In the heart, the role of succinate is unknown. We now report that rat ventricular cardiomyocytes express GPR91. We found that succinate, through GPR91, increases the amplitude and the rate of decline of global Ca(2+) transient, by increasing the phosphorylation levels of ryanodine receptor and phospholamban, two well known Ca(2+) handling proteins. The effects of succinate on Ca(2+) transient were abolished by pre-treatment with adenylyl cyclase and cAMP-dependent protein kinase (PKA) inhibitors. Direct PKA activation by succinate was further confirmed using a FRET-based A-kinase activity reporter. Additionally, succinate decreases cardiomyocyte viability through a caspase-3 activation pathway, effect also prevented by PKA inhibition. Taken together, these observations show that succinate acts as a signaling molecule in cardiomyocytes, modulating global Ca(2+) transient and cell viability through a PKA-dependent pathway. 2009 Elsevier Ltd. All rights reserved.

Bullatacin Triggered ABCB1-Overexpressing Cell Apoptosis via the Mitochondrial-Dependent Pathway

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Yong-Ju Liang

2009-01-01

Full Text Available This paper was to explore bullatacin-mediated multidrug-resistant cell apoptosis at extremely low concentration. To investigate its precise mechanisms, the pathway of cell apoptosis induced by bullatacin was examined. Bullatacin causes an upregulation of ROS and a downregulation of ΔΨm in a concentration-dependent manner in ABCB1-overexpressing KBv200 cells. In addition, cleavers of caspase-9, caspase-3, and PARP were observed following the release of cytochrome c from mitochondria after bullatacin treatment. However, neither cleavage of caspase-8 nor change of expression level of bcl-2, bax and Fas was observed by the same treatment. Pretreating KBv200 cells with N-acetylcysteine, an antioxidant modulator, resulted in a significant reduction of ROS generation and cell apoptosis induced by bullatacin. Bullatacin-induced apoptosis was antagonized by z-LEHD-fmk, a caspase-9 inhibitor, but not by z-IETD-fmk, a caspase-8 inhibitor. These implied that apoptosis of KBv200 cells induced by bullatacin was associated with the mitochondria-dependent pathway that was limited to activation of apical caspase-9.

Backup pathways of NHEJ in cells of higher eukaryotes: Cell cycle dependence

International Nuclear Information System (INIS)

Iliakis, George

2009-01-01

DNA double-strand breaks (DSBs) induced by ionizing radiation (IR) in cells of higher eukaryotes are predominantly repaired by a pathway of non-homologous end joining (NHEJ) utilizing Ku, DNA-PKcs, DNA ligase IV, XRCC4 and XLF/Cernunnos (D-NHEJ) as central components. Work carried out in our laboratory and elsewhere shows that when this pathway is chemically or genetically compromised, cells do not shunt DSBs to homologous recombination repair (HRR) but instead use another form of NHEJ operating as a backup (B-NHEJ). Here I review our efforts to characterize this repair pathway and discuss its dependence on the cell cycle as well as on the growth conditions. I present evidence that B-NHEJ utilizes ligase III, PARP-1 and histone H1. When B-NHEJ is examined throughout the cell cycle, significantly higher activity is observed in G2 phase that cannot be attributed to HRR. Furthermore, the activity of B-NHEJ is compromised when cells enter the plateau phase of growth. Together, these observations uncover a repair pathway with unexpected biochemical constitution and interesting cell cycle and growth factor regulation. They generate a framework for investigating the mechanistic basis of HRR contribution to DSB repair.

A comparative study of manhole hydraulics using stereoscopic PIV and different RANS models.

Science.gov (United States)

Beg, Md Nazmul Azim; Carvalho, Rita F; Tait, Simon; Brevis, Wernher; Rubinato, Matteo; Schellart, Alma; Leandro, Jorge

2017-04-01

Flows in manholes are complex and may include swirling and recirculation flow with significant turbulence and vorticity. However, how these complex 3D flow patterns could generate different energy losses and so affect flow quantity in the wider sewer network is unknown. In this work, 2D3C stereo Particle Image Velocimetry measurements are made in a surcharged scaled circular manhole. A computational fluid dynamics (CFD) model in OpenFOAM ® with four different Reynolds Averaged Navier Stokes (RANS) turbulence model is constructed using a volume of fluid model, to represent flows in this manhole. Velocity profiles and pressure distributions from the models are compared with the experimental data in view of finding the best modelling approach. It was found among four different RANS models that the re-normalization group (RNG) k-ɛ and k-ω shear stress transport (SST) gave a better approximation for velocity and pressure.

Managing the spatial properties and photon correlations in squeezed non-classical twisted light

Science.gov (United States)

Zakharov, R. V.; Tikhonova, O. V.

2018-05-01

Spatial photon correlations and mode content of the squeezed vacuum light generated in a system of two separated nonlinear crystals is investigated. The contribution of both the polar and azimuthal modes with non-zero orbital angular momentum is analyzed. The control and engineering of the spatial properties and degree of entanglement of the non-classical squeezed light by changing the distance between crystals and pump parameters is demonstrated. Methods for amplification of certain spatial modes and managing the output mode content and intensity profile of quantum twisted light are suggested.

The Linear Quadratic Gaussian Multistage Game with Nonclassical Information Pattern Using a Direct Solution Method

Science.gov (United States)

Clemens, Joshua William

Game theory has application across multiple fields, spanning from economic strategy to optimal control of an aircraft and missile on an intercept trajectory. The idea of game theory is fascinating in that we can actually mathematically model real-world scenarios and determine optimal decision making. It may not always be easy to mathematically model certain real-world scenarios, nonetheless, game theory gives us an appreciation for the complexity involved in decision making. This complexity is especially apparent when the players involved have access to different information upon which to base their decision making (a nonclassical information pattern). Here we will focus on the class of adversarial two-player games (sometimes referred to as pursuit-evasion games) with nonclassical information pattern. We present a two-sided (simultaneous) optimization solution method for the two-player linear quadratic Gaussian (LQG) multistage game. This direct solution method allows for further interpretation of each player's decision making (strategy) as compared to previously used formal solution methods. In addition to the optimal control strategies, we present a saddle point proof and we derive an expression for the optimal performance index value. We provide some numerical results in order to further interpret the optimal control strategies and to highlight real-world application of this game-theoretic optimal solution.

Propeller Analysis Using RANS/BEM Coupling Accounting for Blade Blockage

Science.gov (United States)

2015-07-04

are taken into account. It has been implemented using the open source RANS solver OpenFOAM ® and the BEM propeller code PROCAL developed by...Each of these is available in the OpenFOAM mesh data structures. 2.2 Implementation in OpenFOAM In the SIMPLE algorithm as implemented in OpenFOAM ...in OpenFOAM , the source term + must be added to the momentum equations and the source term − to the pressure equation. To apply

RANS Analyses of Turbofan Nozzles with Internal Wedge Deflectors for Noise Reduction

Science.gov (United States)

DeBonis, James R.

2009-01-01

Computational fluid dynamics (CFD) was used to evaluate the flow field and thrust performance of a promising concept for reducing the noise at take-off of dual-stream turbofan nozzles. The concept, offset stream technology, reduces the jet noise observed on the ground by diverting (offsetting) a portion of the fan flow below the core flow, thickening and lengthening this layer between the high-velocity core flow and the ground observers. In this study a wedge placed in the internal fan stream is used as the diverter. Wind, a Reynolds averaged Navier-Stokes (RANS) code, was used to analyze the flow field of the exhaust plume and to calculate nozzle performance. Results showed that the wedge diverts all of the fan flow to the lower side of the nozzle, and the turbulent kinetic energy on the observer side of the nozzle is reduced. This reduction in turbulent kinetic energy should correspond to a reduction in noise. However, because all of the fan flow is diverted, the upper portion of the core flow is exposed to the freestream, and the turbulent kinetic energy on the upper side of the nozzle is increased, creating an unintended noise source. The blockage due to the wedge reduces the fan mass flow proportional to its blockage, and the overall thrust is consequently reduced. The CFD predictions are in very good agreement with experimental flow field data, demonstrating that RANS CFD can accurately predict the velocity and turbulent kinetic energy fields. While this initial design of a large scale wedge nozzle did not meet noise reduction or thrust goals, this study identified areas for improvement and demonstrated that RANS CFD can be used to improve the concept.

Accuracy of the actuator disc-RANS approach for predicting the performance and wake of tidal turbines.

Science.gov (United States)

Batten, W M J; Harrison, M E; Bahaj, A S

2013-02-28

The actuator disc-RANS model has widely been used in wind and tidal energy to predict the wake of a horizontal axis turbine. The model is appropriate where large-scale effects of the turbine on a flow are of interest, for example, when considering environmental impacts, or arrays of devices. The accuracy of the model for modelling the wake of tidal stream turbines has not been demonstrated, and flow predictions presented in the literature for similar modelled scenarios vary significantly. This paper compares the results of the actuator disc-RANS model, where the turbine forces have been derived using a blade-element approach, to experimental data measured in the wake of a scaled turbine. It also compares the results with those of a simpler uniform actuator disc model. The comparisons show that the model is accurate and can predict up to 94 per cent of the variation in the experimental velocity data measured on the centreline of the wake, therefore demonstrating that the actuator disc-RANS model is an accurate approach for modelling a turbine wake, and a conservative approach to predict performance and loads. It can therefore be applied to similar scenarios with confidence.

Numerical prediction of a bulb turbine performance hill chart through RANS simulations

International Nuclear Information System (INIS)

Guénette, V; Houde, S; Ciocan, G D; Deschênes, C; Dumas, G; Huang, J

2012-01-01

Within the framework of an international research consortium on low-head hydraulic turbine flow dynamics, the predictive behavior of Reynolds Averaged Navier-Stokes (RANS) simulations of the efficiency (η) hill chart of a bulb turbine is investigated. The paper presents the impacts of the blade tip gap and the hub gaps on performance predictions.

Application of a New Hybrid RANS/LES Modeling Paradigm to Compressible Flow

Science.gov (United States)

Oliver, Todd; Pederson, Clark; Haering, Sigfried; Moser, Robert

2017-11-01

It is well-known that traditional hybrid RANS/LES modeling approaches suffer from a number of deficiencies. These deficiencies often stem from overly simplistic blending strategies based on scalar measures of turbulence length scale and grid resolution and from use of isotropic subgrid models in LES regions. A recently developed hybrid modeling approach has shown promise in overcoming these deficiencies in incompressible flows [Haering, 2015]. In the approach, RANS/LES blending is accomplished using a hybridization parameter that is governed by an additional model transport equation and is driven to achieve equilibrium between the resolved and unresolved turbulence for the given grid. Further, the model uses an tensor eddy viscosity that is formulated to represent the effects of anisotropic grid resolution on subgrid quantities. In this work, this modeling approach is extended to compressible flows and implemented in the compressible flow solver SU2 (http://su2.stanford.edu/). We discuss both modeling and implementation challenges and show preliminary results for compressible flow test cases with smooth wall separation.

Nonclassical thermal-state superpositions: Analytical evolution law and decoherence behavior

Science.gov (United States)

Meng, Xiang-guo; Goan, Hsi-Sheng; Wang, Ji-suo; Zhang, Ran

2018-03-01

Employing the integration technique within normal products of bosonic operators, we present normal product representations of thermal-state superpositions and investigate their nonclassical features, such as quadrature squeezing, sub-Poissonian distribution, and partial negativity of the Wigner function. We also analytically and numerically investigate their evolution law and decoherence characteristics in an amplitude-decay model via the variations of the probability distributions and the negative volumes of Wigner functions in phase space. The results indicate that the evolution formulas of two thermal component states for amplitude decay can be viewed as the same integral form as a displaced thermal state ρ(V , d) , but governed by the combined action of photon loss and thermal noise. In addition, the larger values of the displacement d and noise V lead to faster decoherence for thermal-state superpositions.

Preface: Nonclassical Transport

International Nuclear Information System (INIS)

Bolshov, L.; Kondratenko, P.; Pruess, K.

2008-01-01

Transport phenomena in highly heterogeneous media can be dramatically different from those in homogeneous media and therefore are of great fundamental and practical interest. Anomalous transport occurs in semiconductor physics, plasma physics, astrophysics, biology, and other areas. It plays an especially important role in hydrogeology because it may govern the rate of migration and degree of dispersion of groundwater contaminants from hazardous waste sites. The series of four articles in this special section of Vadose Zone Journal is devoted to transport phenomena in heterogeneous media in the context of geologic disposal of radioactive waste. It contains the results of joint investigations performed at the Nuclear Safety Institute of the Russian Academy of Sciences and Lawrence Berkeley National Laboratory in California. The work was supported by the U.S. DOE (under Contract No. DEAC02-05CH11231). The problems addressed in this research involve a broad range of space and time scales and were approached using modern methods of theoretical and computational physics, such as scaling analysis and diagrammatic techniques used before in critical phenomena theory. Special attention is paid to the asymptotics of concentration behavior (concentration tails). This issue is exceptionally important for the reliability assessments of radioactive waste disposal because, depending on the structure of the tails, concentrations at large distances from the source can differ by many orders of magnitude. In the first paper of this special section, Bolshov et al. (2008b) present an overview of field and laboratory observations that demonstrate nonclassical flow and transport behavior in geologic media. It is recognized that natural fracture networks as a rule have fractal geometry and can be classified as percolation systems. This is one of the main factors giving rise to anomalous transport in geologic media. Another important factor is the presence of contaminant traps provided by

In vivo FRET imaging revealed a regulatory role of RanGTP in kinetochore-microtubule attachments via Aurora B kinase.

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Yoke-Peng Lee

Full Text Available Under the fluctuating circumstances provided by the innate dynamics of microtubules and opposing tensions resulted from microtubule-associated motors, it is vital to ensure stable kinetochore-microtubule attachments for accurate segregation. However, a comprehensive understanding of how this regulation is mechanistically achieved remains elusive. Using our newly designed live cell FRET time-lapse imaging, we found that post-metaphase RanGTP is crucial in the maintenance of stable kinetochore-microtubule attachments by regulating Aurora B kinase via the NES-bearing Mst1. More importantly, our study demonstrates that by ensuring stable alignment of metaphase chromosomes prior to segregation, RanGTP is indispensible in governing the genomic integrity and the fidelity of cell cycle progression. Our findings suggest an additional role of RanGTP beyond its known function in mitotic spindle assembly during the prometaphase-metaphase transition.

From DNS to RANS: A Multi-model workflow to understand the Influence of Hurricanes on Generating Turbidity Currents in the Gulf of Mexico

Science.gov (United States)

Syvitski, J. P.; Arango, H.; Harris, C. K.; Meiburg, E. H.; Jenkins, C. J.; Auad, G.; Hutton, E.; Kniskern, T. A.; Radhakrishnan, S.

2016-12-01

A loosely coupled numerical workflow is developed to address land-sea pathways for sediment routing from terrestrial and coastal sources, across the continental shelf and ultimately down the continental slope canyon system of the northern Gulf of Mexico (GOM). Model simulations represent a range of environmental conditions that might lead to the generation of turbidity-currents. The workflow comprises: 1) A simulator for the water and sediment discharged from rivers into the GOM with WMBsedv2 with calibration using USGS and USACE gauged river data; 2) Domain grids and bathymetry (ETOPO2) for the ocean models and realistic seabed sediment texture grids (dbSEABED) for the sediment transport models; 3) A spectral wave action simulator (10 km resolution) (WaveWatch III) driven by GFDL - GFS winds; 4) A simulator for ocean dynamics (ROMS) forced with ECMWF ERA winds; 5) A simulator for seafloor resuspension and transport (CSTMS); 6) Simulators (HurriSlip) of seafloor failure and flow ignition locations for boundary input to a turbidity current model; and 7) A RANS turbidity current model (TURBINS) to route sediment flows down GOM canyons, providing estimates of bottom shear stresses. TURBINS was developed first as a DNS model and then converted to an LES model wherein a dynamic turbulence closure scheme was employed. Like most DNS to LES model comparisons (these being done by the UCSB team), turbulence scaling allowed for higher Re applications but were found still not capable of simulating field scale (GOM continental canyons) environments. The LES model was next converted to a non-hydrostatic RANS model capable of field scale applications but only with a daisy-chain approach to multiple model runs along the simulated canyon floor. These model adaptations allowed the workflow to be tested for the year 1-Oct-2007 to 30-Sep-2008 that included two domain Hurricanes (Ike and Gustav). The RANS-TURBINS employed further boundary simplifications on both sediment erosion and

Prediction of dosage-based parameters from the puff dispersion of airborne materials in urban environments using the CFD-RANS methodology

Science.gov (United States)

Efthimiou, G. C.; Andronopoulos, S.; Bartzis, J. G.

2018-02-01

One of the key issues of recent research on the dispersion inside complex urban environments is the ability to predict dosage-based parameters from the puff release of an airborne material from a point source in the atmospheric boundary layer inside the built-up area. The present work addresses the question of whether the computational fluid dynamics (CFD)-Reynolds-averaged Navier-Stokes (RANS) methodology can be used to predict ensemble-average dosage-based parameters that are related with the puff dispersion. RANS simulations with the ADREA-HF code were, therefore, performed, where a single puff was released in each case. The present method is validated against the data sets from two wind-tunnel experiments. In each experiment, more than 200 puffs were released from which ensemble-averaged dosage-based parameters were calculated and compared to the model's predictions. The performance of the model was evaluated using scatter plots and three validation metrics: fractional bias, normalized mean square error, and factor of two. The model presented a better performance for the temporal parameters (i.e., ensemble-average times of puff arrival, peak, leaving, duration, ascent, and descent) than for the ensemble-average dosage and peak concentration. The majority of the obtained values of validation metrics were inside established acceptance limits. Based on the obtained model performance indices, the CFD-RANS methodology as implemented in the code ADREA-HF is able to predict the ensemble-average temporal quantities related to transient emissions of airborne material in urban areas within the range of the model performance acceptance criteria established in the literature. The CFD-RANS methodology as implemented in the code ADREA-HF is also able to predict the ensemble-average dosage, but the dosage results should be treated with some caution; as in one case, the observed ensemble-average dosage was under-estimated slightly more than the acceptance criteria. Ensemble

The Interaction of a N-Type Four Level Atom with the Electromagnetic Field for a Kerr Medium Induced Intensity-Dependent Coupling

Science.gov (United States)

Othman, Anas; Yevick, David

2018-01-01

The interaction of a N-type four-level atom with a single field in the presence of an intensity-dependent coupling in a nonlinear Kerr medium is investigated. The exact analytic solution is obtained in the case that the atom and electromagnetic field are initially in a higher excited state and a coherent state, respectively. It is then demonstrated that effects such as nonclassical light generation, degree of entanglement stabilization, Kerr medium nonclassical control, and squeezed light are can be more efficiently implemented within this four-level framework than in many competing procedures. Additionally, inversion, linear entropy, Mandel Q-parameter and normal squeezing dynamics are examined.

Essential role of TGF-beta/Smad pathway on statin dependent vascular smooth muscle cell regulation.

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Juan Rodríguez-Vita

Full Text Available BACKGROUND: The 3-hydroxy-3-methylglutaryl CoA reductase inhibitors (also called statins exert proven beneficial effects on cardiovascular diseases. Recent data suggest a protective role for Transforming Growth Factor-beta (TGF-beta in atherosclerosis by regulating the balance between inflammation and extracellular matrix accumulation. However, there are no studies about the effect of statins on TGF-beta/Smad pathway in atherosclerosis and vascular cells. METHODOLOGY: In cultured vascular smooth muscle cells (VSMCs statins enhanced Smad pathway activation caused by TGF-beta. In addition, statins upregulated TGF-beta receptor type II (TRII, and increased TGF-beta synthesis and TGF-beta/Smad-dependent actions. In this sense, statins, through Smad activation, render VSMCs more susceptible to TGF-beta induced apoptosis and increased TGF-beta-mediated ECM production. It is well documented that high doses of statins induce apoptosis in cultured VSMC in the presence of serum; however the precise mechanism of this effect remains to be elucidated. We have found that statins-induced apoptosis was mediated by TGF-beta/Smad pathway. Finally, we have described that RhoA inhibition is a common intracellular mechanisms involved in statins effects. The in vivo relevance of these findings was assessed in an experimental model of atherosclerosis in apolipoprotein E deficient mice: Treatment with Atorvastatin increased Smad3 phosphorylation and TRII overexpression, associated to elevated ECM deposition in the VSMCs within atheroma plaques, while apoptosis was not detected. CONCLUSIONS: Statins enhance TGF-beta/Smad pathway, regulating ligand levels, receptor, main signaling pathway and cellular responses of VSMC, including apoptosis and ECM accumulation. Our findings show that TGF-beta/Smad pathway is essential for statins-dependent actions in VSMCs.

Nucleolus-derived mediators in oncogenic stress response and activation of p53-dependent pathways.

Science.gov (United States)

Stępiński, Dariusz

2016-08-01

Rapid growth and division of cells, including tumor ones, is correlated with intensive protein biosynthesis. The output of nucleoli, organelles where translational machineries are formed, depends on a rate of particular stages of ribosome production and on accessibility of elements crucial for their effective functioning, including substrates, enzymes as well as energy resources. Different factors that induce cellular stress also often lead to nucleolar dysfunction which results in ribosome biogenesis impairment. Such nucleolar disorders, called nucleolar or ribosomal stress, usually affect cellular functioning which in fact is a result of p53-dependent pathway activation, elicited as a response to stress. These pathways direct cells to new destinations such as cell cycle arrest, damage repair, differentiation, autophagy, programmed cell death or aging. In the case of impaired nucleolar functioning, nucleolar and ribosomal proteins mediate activation of the p53 pathways. They are also triggered as a response to oncogenic factor overexpression to protect tissues and organs against extensive proliferation of abnormal cells. Intentional impairment of any step of ribosome biosynthesis which would direct the cells to these destinations could be a strategy used in anticancer therapy. This review presents current knowledge on a nucleolus, mainly in relation to cancer biology, which is an important and extremely sensitive element of the mechanism participating in cellular stress reaction mediating activation of the p53 pathways in order to counteract stress effects, especially cancer development.

Nonclassic congenital adrenal hyperplasia misdiagnosed as Turner syndrome

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Vineet V Mishra

2015-01-01

Full Text Available We present a patient with nonclassic congenital adrenal hyperplasia (NCAH misdiagnosed as mosaic Turner syndrome. She presented with complaints of primary infertility. Short stature, the presence of facial hair and hoarse voice was also noted. She had primary amenorrhea and was advised for karyotype at 16 years of age, which was reported as 45, X[20]/46, XX[80], stating her as a case of mosaic Turner syndrome. Clitoroplasty was done at 21 years of age for clitoromegaly, which was noticed during puberty. The diagnosis of mosaic Turner could not explain the virilization. Therefore, we repeated the karyotype, which revealed 46, XX in more than 100 metaphases and was sufficient to exclude mosaicism. Furthermore, the endocrinological evaluation revealed high testosterone level with a normal 17 alpha-hydroxyprogesterone (17-OHP. The presence of pubertal onset virilization with a karyotype of 46, XX and raised testosterone level with normal 17-OHP level, raised the suspicion of NCAH for which adrenocorticotropic hormone stimulation test was done which confirmed the diagnosis of NCAH.

Non-Classical Gluconeogenesis-Dependent Glucose Metabolism in Rhipicephalus microplus Embryonic Cell Line BME26

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Renato Martins da Silva

2015-01-01

Full Text Available In this work we evaluated several genes involved in gluconeogenesis, glycolysis and glycogen metabolism, the major pathways for carbohydrate catabolism and anabolism, in the BME26 Rhipicephalus microplus embryonic cell line. Genetic and catalytic control of the genes and enzymes associated with these pathways are modulated by alterations in energy resource availability (primarily glucose. BME26 cells in media were investigated using three different glucose concentrations, and changes in the transcription levels of target genes in response to carbohydrate utilization were assessed. The results indicate that several genes, such as glycogen synthase (GS, glycogen synthase kinase 3 (GSK3, phosphoenolpyruvate carboxykinase (PEPCK, and glucose-6 phosphatase (GP displayed mutual regulation in response to glucose treatment. Surprisingly, the transcription of gluconeogenic enzymes was found to increase alongside that of glycolytic enzymes, especially pyruvate kinase, with high glucose treatment. In addition, RNAi data from this study revealed that the transcription of gluconeogenic genes in BME26 cells is controlled by GSK-3. Collectively, these results improve our understanding of how glucose metabolism is regulated at the genetic level in tick cells.

Arctigenin Inhibits Osteoclast Differentiation and Function by Suppressing Both Calcineurin-Dependent and Osteoblastic Cell-Dependent NFATc1 Pathways

OpenAIRE

Yamashita, Teruhito; Uehara, Shunsuke; Udagawa, Nobuyuki; Li, Feng; Kadota, Shigetoshi; Esumi, Hiroyasu; Kobayashi, Yasuhiro; Takahashi, Naoyuki

2014-01-01

Arctigenin, a lignan-derived compound, is a constituent of the seeds of Arctium lappa. Arctigenin was previously shown to inhibit osteoclastogenesis; however, this inhibitory mechanism has yet to be elucidated. Here, we showed that arctigenin inhibited the action of nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1), a key transcription factor for osteoclastogenesis. NFATc1 in osteoclast precursors was activated through two distinct pathways: the calcineurin-dependent and osteoblasti...

A non-canonical RNA degradation pathway suppresses RNAi-dependent epimutations in the human fungal pathogen Mucor circinelloides.

Science.gov (United States)

Calo, Silvia; Nicolás, Francisco E; Lee, Soo Chan; Vila, Ana; Cervantes, Maria; Torres-Martinez, Santiago; Ruiz-Vazquez, Rosa M; Cardenas, Maria E; Heitman, Joseph

2017-03-01

Mucorales are a group of basal fungi that includes the casual agents of the human emerging disease mucormycosis. Recent studies revealed that these pathogens activate an RNAi-based pathway to rapidly generate drug-resistant epimutant strains when exposed to stressful compounds such as the antifungal drug FK506. To elucidate the molecular mechanism of this epimutation pathway, we performed a genetic analysis in Mucor circinelloides that revealed an inhibitory role for the non-canonical RdRP-dependent Dicer-independent silencing pathway, which is an RNAi-based mechanism involved in mRNA degradation that was recently identified. Thus, mutations that specifically block the mRNA degradation pathway, such as those in the genes r3b2 and rdrp3, enhance the production of drug resistant epimutants, similar to the phenotype previously described for mutation of the gene rdrp1. Our genetic analysis also revealed two new specific components of the epimutation pathway related to the quelling induced protein (qip) and a Sad-3-like helicase (rnhA), as mutations in these genes prevented formation of drug-resistant epimutants. Remarkably, drug-resistant epimutant production was notably increased in M. circinelloides f. circinelloides isolates from humans or other animal hosts. The host-pathogen interaction could be a stressful environment in which the phenotypic plasticity provided by the epimutant pathway might provide an advantage for these strains. These results evoke a model whereby balanced regulation of two different RNAi pathways is determined by the activation of the RNAi-dependent epimutant pathway under stress conditions, or its repression when the regular maintenance of the mRNA degradation pathway operates under non-stress conditions.

A non-canonical RNA degradation pathway suppresses RNAi-dependent epimutations in the human fungal pathogen Mucor circinelloides.

Directory of Open Access Journals (Sweden)

Silvia Calo

2017-03-01

Full Text Available Mucorales are a group of basal fungi that includes the casual agents of the human emerging disease mucormycosis. Recent studies revealed that these pathogens activate an RNAi-based pathway to rapidly generate drug-resistant epimutant strains when exposed to stressful compounds such as the antifungal drug FK506. To elucidate the molecular mechanism of this epimutation pathway, we performed a genetic analysis in Mucor circinelloides that revealed an inhibitory role for the non-canonical RdRP-dependent Dicer-independent silencing pathway, which is an RNAi-based mechanism involved in mRNA degradation that was recently identified. Thus, mutations that specifically block the mRNA degradation pathway, such as those in the genes r3b2 and rdrp3, enhance the production of drug resistant epimutants, similar to the phenotype previously described for mutation of the gene rdrp1. Our genetic analysis also revealed two new specific components of the epimutation pathway related to the quelling induced protein (qip and a Sad-3-like helicase (rnhA, as mutations in these genes prevented formation of drug-resistant epimutants. Remarkably, drug-resistant epimutant production was notably increased in M. circinelloides f. circinelloides isolates from humans or other animal hosts. The host-pathogen interaction could be a stressful environment in which the phenotypic plasticity provided by the epimutant pathway might provide an advantage for these strains. These results evoke a model whereby balanced regulation of two different RNAi pathways is determined by the activation of the RNAi-dependent epimutant pathway under stress conditions, or its repression when the regular maintenance of the mRNA degradation pathway operates under non-stress conditions.

Pathways of the inferior frontal occipital fasciculus in overt speech and reading.

Science.gov (United States)

Rollans, Claire; Cheema, Kulpreet; Georgiou, George K; Cummine, Jacqueline

2017-11-19

In this study, we examined the relationship between tractography-based measures of white matter integrity (ex. fractional anisotropy [FA]) from diffusion tensor imaging (DTI) and five reading-related tasks, including rapid automatized naming (RAN) of letters, digits, and objects, and reading of real words and nonwords. Twenty university students with no reported history of reading difficulties were tested on all five tasks and their performance was correlated with diffusion measures extracted through DTI tractography. A secondary analysis using whole-brain Tract-Based Spatial Statistics (TBSS) was also used to find clusters showing significant negative correlations between reaction time and FA. Results showed a significant relationship between the left inferior fronto-occipital fasciculus FA and performance on the RAN of objects task, as well as a strong relationship to nonword reading, which suggests a role for this tract in slower, non-automatic and/or resource-demanding speech tasks. There were no significant relationships between FA and the faster, more automatic speech tasks (RAN of letters and digits, and real word reading). These findings provide evidence for the role of the inferior fronto-occipital fasciculus in tasks that are highly demanding of orthography-phonology translation (e.g., nonword reading) and semantic processing (e.g., RAN object). This demonstrates the importance of the inferior fronto-occipital fasciculus in basic naming and suggests that this tract may be a sensitive predictor of rapid naming performance within the typical population. We discuss the findings in the context of current models of reading and speech production to further characterize the white matter pathways associated with basic reading processes. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Turbulence-induced heat transfer in PBMR core using LES and RANS

International Nuclear Information System (INIS)

Lee, Jung-Jae; Yoon, Su-Jong; Park, Goon-Cherl; Lee, Won-Jae

2007-01-01

This paper introduces the results of numerical simulations on flow fields and relevant heat transfer in the pebble bed reactor (PBR) core, since the coolant passes a highly complicated random flow path with a high Reynolds number, an appropriate treatment of the turbulence is required. A set of simple experiments for the flow over a circular cylinder with heat transfer was conducted to finally select the large eddy simulation (LES) and k-ω model among the considering Reynolds-averaged Navier-Stokes (RANS) models for PBR application. Using these models, the PBR cores, whose geometries were simplified to the body-centered cubical (BCC) and face-centered cubical (FCC) structures, were simulated. A larger pressure drop, a more random flow field, a higher vorticity magnitude and a higher temperature at the local hot spots on the pebble surface were found in the results of the LES than in those of RANS for both geometries. In cases of the LES, the flow structures were resolved up to the grid scales. Irregular distributions of the flow and local heat transfer were found in the BCC core, while relatively regular distributions for the FCC core. The turbulent nature of the coolant flow in the pebble core evidently affected the fuel surface temperature distribution. (author)

Non-classic multiscale modeling of manipulation based on AFM, in aqueous and humid ambient

Science.gov (United States)

Korayem, M. H.; Homayooni, A.; Hefzabad, R. N.

2018-05-01

To achieve a precise manipulation, it is important that an accurate model consisting the size effect and environmental conditions be employed. In this paper, the non-classical multiscale modeling is developed to investigate the manipulation in a vacuum, aqueous and humid ambient. The manipulation structure is considered into two parts as a macro-field (MF) and a nano-field (NF). The governing equations of the AFM components (consist of the cantilever and tip) in the MF are derived based on the modified couple stress theory. The material length scale parameter is used to study the size effect. The fluid flow in the MF is assumed as the Couette and Creeping flows. Moreover, the NF is modeled using the molecular dynamics. The Electro-Based (ELBA) model is considered to model the ambient condition in the NF. The nanoparticle in the different conditions is taken into account to study the manipulation. The results of the manipulation indicate that the predicted deflection of the non-classical model is less than the classical one. Comparison of the nanoparticle travelled distance on substrate shows that the manipulation in the submerged condition is close to the ideal manipulation. The results of humid condition illustrate that by increasing the relative humidity (RH) the manipulation force decreases. Furthermore, Root Mean Square (RMS) as a criterion of damage demonstrates that the submerged nanoparticle has the minimum damage, however, the minimum manipulation force occurs in superlative humid ambient.

Cost-effective resource allocation in C-RAN with mobile cloud

OpenAIRE

Wang, Kezhi; Yang, Kun; Wang, Xinhou; Magurawalage, Chathura Sarathchandra

2016-01-01

Taking full advantages of two cloud-based techniques, i.e., cloud radio access network (C-RAN) and mobile cloud computing (MCC), mobile operators will be able to provide the good service to the mobile user as well as increasing their revenue. This paper aims to minimize the mobile operator's cost while at the same time, meet the task time constraints of the mobile users. In particular, we assume that the mobile cloud first completes the tasks for the mobile user and then transmits the results...

Nonclassical polarization effects in fluorescence emission spectra from microdroplets

Science.gov (United States)

Arnold, S.; Goddard, N. L.; Hill, S. C.

1999-12-01

We report a pronounced nonclassical polarization effect on the shape of fluorescence emission spectra from isolated microdroplets containing a dilute solution of soluble fluors or a dilute layer of surfactant fluors. We see different spectral shapes for 90° scattering when comparing between IVV, IVH, IHH, IHV. However, we measure the largest difference in spectral shape in the surfactant case, with the incident polarization directed toward the detector (IHV vs IHH). Imaging reveals that the emission in this case principally arises from two distinct regions near the surface of the droplet, which are diametrically opposed and along the axis of the incident laser beam. The effect appears to be the direct result of coupling between molecular emission moments and electromagnetic modes of the droplet. It is not the molecule which radiates but the molecule microvessel. Directional emission is sensitive to the polarization of the electromagnetic mode which is stimulated by the coupling.

Evaluating C-RAN Fronthaul Functional Splits in Terms of Network Level Energy and Cost Savings

DEFF Research Database (Denmark)

Checko, Aleksandra; Popovska Avramova, Andrijana; Berger, Michael Stübert

2016-01-01

The placement of the complete baseband processing in a centralized pool results in high data rate requirement and inflexibility of the fronthaul network, which challenges the energy and cost effectiveness of the cloud radio access network (C-RAN). Recently, redesign of the C-RAN through functional...... split in the baseband processing chain has been proposed to overcome these challenges. This paper evaluates, by mathematical and simulation methods, different splits with respect to network level energy and cost efficiency having in the mind the expected quality of service.The proposed mathematical...... model quantifies the multiplexing gains and the trade-offs between centralization and decentralization concerning the cost of the pool, fronthaul network capacity and resource utilization. The event-based simulation captures the influence of the traffic load dynamics and traffic type variation...

Dependency of a therapy-resistant state of cancer cells on a lipid peroxidase pathway.

Science.gov (United States)

Viswanathan, Vasanthi S; Ryan, Matthew J; Dhruv, Harshil D; Gill, Shubhroz; Eichhoff, Ossia M; Seashore-Ludlow, Brinton; Kaffenberger, Samuel D; Eaton, John K; Shimada, Kenichi; Aguirre, Andrew J; Viswanathan, Srinivas R; Chattopadhyay, Shrikanta; Tamayo, Pablo; Yang, Wan Seok; Rees, Matthew G; Chen, Sixun; Boskovic, Zarko V; Javaid, Sarah; Huang, Cherrie; Wu, Xiaoyun; Tseng, Yuen-Yi; Roider, Elisabeth M; Gao, Dong; Cleary, James M; Wolpin, Brian M; Mesirov, Jill P; Haber, Daniel A; Engelman, Jeffrey A; Boehm, Jesse S; Kotz, Joanne D; Hon, Cindy S; Chen, Yu; Hahn, William C; Levesque, Mitchell P; Doench, John G; Berens, Michael E; Shamji, Alykhan F; Clemons, Paul A; Stockwell, Brent R; Schreiber, Stuart L

2017-07-27

Plasticity of the cell state has been proposed to drive resistance to multiple classes of cancer therapies, thereby limiting their effectiveness. A high-mesenchymal cell state observed in human tumours and cancer cell lines has been associated with resistance to multiple treatment modalities across diverse cancer lineages, but the mechanistic underpinning for this state has remained incompletely understood. Here we molecularly characterize this therapy-resistant high-mesenchymal cell state in human cancer cell lines and organoids and show that it depends on a druggable lipid-peroxidase pathway that protects against ferroptosis, a non-apoptotic form of cell death induced by the build-up of toxic lipid peroxides. We show that this cell state is characterized by activity of enzymes that promote the synthesis of polyunsaturated lipids. These lipids are the substrates for lipid peroxidation by lipoxygenase enzymes. This lipid metabolism creates a dependency on pathways converging on the phospholipid glutathione peroxidase (GPX4), a selenocysteine-containing enzyme that dissipates lipid peroxides and thereby prevents the iron-mediated reactions of peroxides that induce ferroptotic cell death. Dependency on GPX4 was found to exist across diverse therapy-resistant states characterized by high expression of ZEB1, including epithelial-mesenchymal transition in epithelial-derived carcinomas, TGFβ-mediated therapy-resistance in melanoma, treatment-induced neuroendocrine transdifferentiation in prostate cancer, and sarcomas, which are fixed in a mesenchymal state owing to their cells of origin. We identify vulnerability to ferroptic cell death induced by inhibition of a lipid peroxidase pathway as a feature of therapy-resistant cancer cells across diverse mesenchymal cell-state contexts.

Analysis of the elastic behaviour of nonclassical nonlinear mesoscopic materials in quasi-static experiments

International Nuclear Information System (INIS)

Ruffino, E.; Scalerandi, M.

2000-01-01

As discovered by recent quasi-static and dynamic resonance experiments, the classical nonlinear theory fails in describing the hysteretic behaviour of nonlinear mesoscopic materials like rocks, concrete, etc. The paper applies the local interaction simulation approach (LISA) for studying such kind of nonclassical nonlinearity. To this purpose, in the LISA treatment of ultrasonic wave propagation has been included a phenomenological model, based on the PM space approach, of the local mesoscopic features of rocks and other materials with localized damages. A quantitative comparison of simulation and experimental results in quasi-static experiments is also presented

I RAN Fast and I Remembered What I Read: The Relationship between Reading, Rapid Automatic Naming, and Auditory and Visual Short-Term Memory

Directory of Open Access Journals (Sweden)

Sheila G. Crewther

2011-05-01

Full Text Available Although rapid automatic naming (RAN speed and short-term auditory memory are widely recognised as good predictors of reading ability in most age groups, the predictive value of short-term memory for visually presented digits for reading and RAN in young typically developing learner readers (mean age 91.5 months has seldom been investigated. We found that visual digit span is a better predictor of reading ability than auditory digit span in learner readers. A significant correlation has also been found between RAN speed and visual, but not auditory digit span. These results suggests that RAN speed may be a good predictor of a child's future reading ability and eventual fluency because like visual digit span, it is a measure of rate of access to memory for the visual icons and their semantic name and meaning. The results also suggest that auditory memory is not an important factor in young children learning to read.

Expression and phylogenetic analyses reveal paralogous lineages of putatively classical and non-classical MHC-I genes in three sparrow species (Passer).

Science.gov (United States)

Drews, Anna; Strandh, Maria; Råberg, Lars; Westerdahl, Helena

2017-06-26

The Major Histocompatibility Complex (MHC) plays a central role in immunity and has been given considerable attention by evolutionary ecologists due to its associations with fitness-related traits. Songbirds have unusually high numbers of MHC class I (MHC-I) genes, but it is not known whether all are expressed and equally important for immune function. Classical MHC-I genes are highly expressed, polymorphic and present peptides to T-cells whereas non-classical MHC-I genes have lower expression, are more monomorphic and do not present peptides to T-cells. To get a better understanding of the highly duplicated MHC genes in songbirds, we studied gene expression in a phylogenetic framework in three species of sparrows (house sparrow, tree sparrow and Spanish sparrow), using high-throughput sequencing. We hypothesize that sparrows could have classical and non-classical genes, as previously indicated though never tested using gene expression. The phylogenetic analyses reveal two distinct types of MHC-I alleles among the three sparrow species, one with high and one with low level of polymorphism, thus resembling classical and non-classical genes, respectively. All individuals had both types of alleles, but there was copy number variation both within and among the sparrow species. However, the number of highly polymorphic alleles that were expressed did not vary between species, suggesting that the structural genomic variation is counterbalanced by conserved gene expression. Overall, 50% of the MHC-I alleles were expressed in sparrows. Expression of the highly polymorphic alleles was very variable, whereas the alleles with low polymorphism had uniformly low expression. Interestingly, within an individual only one or two alleles from the polymorphic genes were highly expressed, indicating that only a single copy of these is highly expressed. Taken together, the phylogenetic reconstruction and the analyses of expression suggest that sparrows have both classical and non-classical

Evolution and variability of Solanum RanGAP2, a cofactor in the incompatible interaction between the resistance protein GPA2 and the Globodera pallida effector Gp-RBP-1.

Science.gov (United States)

Carpentier, Jean; Grenier, Eric; Esquibet, Magalie; Hamel, Louis-Philippe; Moffett, Peter; Manzanares-Dauleux, Maria J; Kerlan, Marie-Claire

2013-04-19

The Ran GTPase Activating Protein 2 (RanGAP2) was first described as a regulator of mitosis and nucleocytoplasmic trafficking. It was then found to interact with the Coiled-Coil domain of the Rx and GPA2 resistance proteins, which confer resistance to Potato Virus X (PVX) and potato cyst nematode Globodera pallida, respectively. RanGAP2 is thought to mediate recognition of the avirulence protein GP-RBP-1 by GPA2. However, the Gpa2-induced hypersensitive response appears to be relatively weak and Gpa2 is limited in terms of spectrum of efficiency as it is effective against only two nematode populations. While functional and evolutionary analyses of Gp-Rbp-1 and Gpa2 identified key residues in both the resistance and avirulence proteins that are involved in recognition determination, whether variation in RanGAP2 also plays a role in pathogen recognition has not been investigated. We amplified a total of 147 RanGAP2 sequences from 55 accessions belonging to 18 different di-and tetraploid Solanum species from the section Petota. Among the newly identified sequences, 133 haplotypes were obtained and 19.1% of the nucleotide sites were found to be polymorphic. The observed intra-specific nucleotide diversity ranges from 0.1 to 1.3%. Analysis of the selection pressures acting on RanGAP2 suggests that this gene evolved mainly under purifying selection. Nonetheless, we identified polymorphic positions in the protein sequence at the intra-specific level, which could modulate the activity of RanGAP2. Two polymorphic sites and a three amino-acid deletion in RanGAP2 were found to affect the timing and intensity of the Gpa2-induced hypersensitive response to avirulent GP-RBP-1 variants even though they did not confer any gain of recognition of virulent GP-RBP-1 variants. Our results highlight how a resistance gene co-factor can manage in terms of evolution both an established role as a cell housekeeping gene and an implication in plant parasite interactions. StRanGAP2 gene

Functional Relevance of Different Basal Ganglia Pathways Investigated in a Spiking Model with Reward Dependent Plasticity

Directory of Open Access Journals (Sweden)

Pierre Berthet

2016-07-01

Full Text Available The brain enables animals to behaviourally adapt in order to survive in a complex and dynamic environment, but how reward-oriented behaviours are achieved and computed by its underlying neural circuitry is an open question. To address this concern, we have developed a spiking model of the basal ganglia (BG that learns to dis-inhibit the action leading to a reward despite ongoing changes in the reward schedule. The architecture of the network features the two pathways commonly described in BG, the direct (denoted D1 and the indirect (denoted D2 pathway, as well as a loop involving striatum and the dopaminergic system. The activity of these dopaminergic neurons conveys the reward prediction error (RPE, which determines the magnitude of synaptic plasticity within the different pathways. All plastic connections implement a versatile four-factor learning rule derived from Bayesian inference that depends upon pre- and postsynaptic activity, receptor type and dopamine level. Synaptic weight updates occur in the D1 or D2 pathways depending on the sign of the RPE, and an efference copy informs upstream nuclei about the action selected. We demonstrate successful performance of the system in a multiple-choice learning task with a transiently changing reward schedule. We simulate lesioning of the various pathways and show that a condition without the D2 pathway fares worse than one without D1. Additionally, we simulate the degeneration observed in Parkinson’s disease (PD by decreasing the number of dopaminergic neurons during learning. The results suggest that the D1 pathway impairment in PD might have been overlooked. Furthermore, an analysis of the alterations in the synaptic weights shows that using the absolute reward value instead of the RPE leads to a larger change in D1.

SUMO modification through rapamycin-mediated heterodimerization reveals a dual role for Ubc9 in targeting RanGAP1 to nuclear pore complexes

International Nuclear Information System (INIS)

Zhu Shanshan; Zhang Hong; Matunis, Michael J.

2006-01-01

SUMOs (small ubiquitin-related modifiers) are eukaryotic proteins that are covalently conjugated to other proteins and thereby regulate a wide range of important cellular processes. The molecular mechanisms by which SUMO modification influences the functions of most target proteins and cellular processes, however, remain poorly defined. A major obstacle to investigating the effects of SUMO modification is the availability of a system for selectively inducing the modification or demodification of an individual protein. To address this problem, we have developed a procedure using the rapamycin heterodimerizer system. This procedure involves co-expression of rapamycin-binding domain fusion proteins of SUMO and candidate SUMO substrates in living cells. Treating cells with rapamycin induces a tight association between SUMO and a single SUMO substrate, thereby allowing specific downstream effects to be analyzed. Using RanGAP1 as a model SUMO substrate, the heterodimerizer system was used to investigate the molecular mechanism by which SUMO modification targets RanGAP1 from the cytoplasm to nuclear pore complexes (NPCs). Our results revealed a dual role for Ubc9 in targeting RanGAP1 to NPCs: In addition to conjugating SUMO-1 to RanGAP1, Ubc9 is also required to form a stable ternary complex with SUMO-1 modified RanGAP1 and Nup358. As illustrated by our studies, the rapamycin heterodimerizer system represents a novel tool for studying the molecular effects of SUMO modification

Evaluation of RANS and LES models for Natural Convection in High-Aspect-Ratio Parallel Plate Channels

Science.gov (United States)

Fradeneck, Austen; Kimber, Mark

2017-11-01

The present study evaluates the effectiveness of current RANS and LES models in simulating natural convection in high-aspect ratio parallel plate channels. The geometry under consideration is based on a simplification of the coolant and bypass channels in the very high-temperature gas reactor (VHTR). Two thermal conditions are considered, asymmetric and symmetric wall heating with an applied heat flux to match Rayleigh numbers experienced in the VHTR during a loss of flow accident (LOFA). RANS models are compared to analogous high-fidelity LES simulations. Preliminary results demonstrate the efficacy of the low-Reynolds number k- ɛ formulations and their enhancement to the standard form and Reynolds stress transport model in terms of calculating the turbulence production due to buoyancy and overall mean flow variables.

Antibodies induced by vaccination with purified chick embryo cell culture vaccine (PCECV) cross-neutralize non-classical bat lyssavirus strains.

Science.gov (United States)

Malerczyk, Claudius; Selhorst, Thomas; Tordo, Noël; Moore, Susan; Müller, Thomas

2009-08-27

Tissue-culture vaccines like purified chick embryo cell vaccine (PCECV) have been shown to provide protection against classical rabies virus (RABV) via pre-exposure or post-exposure prophylaxis. A cross-neutralization study was conducted using a panel of 100 human sera, to determine, to what extent after vaccination with PCECV protection exists against non-classical bat lyssavirus strains like European bat lyssavirus (EBLV) type 1 and 2 and Australian bat lyssavirus (ABLV). Virus neutralizing antibody (VNA) concentrations against the rabies virus variants CVS-11, ABLV, EBLV-1 and EBLV-2 were determined by using a modified rapid fluorescent focus inhibition test. For ABLV and EBLV-2, the comparison to CVS-11 revealed almost identical results (100% adequate VNA concentrations >or=0.5 IU/mL; correlation coefficient r(2)=0.69 and 0.77, respectively), while for EBLV-1 more scattering was observed (97% adequate VNA concentrations; r(2)=0.50). In conclusion, vaccination with PCECV produces adequate VNA concentrations against classical RABV as well as non-classical lyssavirus strains ABLV, EBLV-1, and EBLV-2.

Regulator of calcineurin 1 differentially regulates TLR-dependent MyD88 and TRIF signaling pathways.

Directory of Open Access Journals (Sweden)

Zheng Pang

Full Text Available Toll-like receptors (TLRs recognize the conserved molecular patterns in microorganisms and trigger myeloid differentiation primary response 88 (MyD88 and/or TIR-domain-containing adapter-inducing interferon-β (TRIF pathways that are critical for host defense against microbial infection. However, the molecular mechanisms that govern TLR signaling remain incompletely understood. Regulator of calcineurin-1 (RCAN1, a small evolutionarily conserved protein that inhibits calcineurin phosphatase activity, suppresses inflammation during Pseudomonas aeruginosa infection. Here, we define the roles for RCAN1 in P. aeruginosa lipopolysaccharide (LPS-activated TLR4 signaling. We compared the effects of P. aeruginosa LPS challenge on bone marrow-derived macrophages from both wild-type and RCAN1-deficient mice and found that RCAN1 deficiency increased the MyD88-NF-κB-mediated cytokine production (IL-6, TNF and MIP-2, whereas TRIF-interferon-stimulated response elements (ISRE-mediated cytokine production (IFNβ, RANTES and IP-10 was suppressed. RCAN1 deficiency caused increased IκBα phosphorylation and NF-κB activity in the MyD88-dependent pathway, but impaired ISRE activation and reduced IRF7 expression in the TRIF-dependent pathway. Complementary studies of a mouse model of P. aeruginosa LPS-induced acute pneumonia confirmed that RCAN1-deficient mice displayed greatly enhanced NF-κB activity and MyD88-NF-κB-mediated cytokine production, which correlated with enhanced pulmonary infiltration of neutrophils. By contrast, RCAN1 deficiency had little effect on the TRIF pathway in vivo. These findings demonstrate a novel regulatory role of RCAN1 in TLR signaling, which differentially regulates MyD88 and TRIF pathways.

Alternative pathways of thromboplastin-dependent activation of human factor X in plasma

International Nuclear Information System (INIS)

Marlar, R.A.; Griffin, J.H.

1981-01-01

To determine the interrelationships of the major coagulation pathways, the activation of 3H-labeled factor X in normal and various deficient human plasmas was evaluated when clotting was triggered by dilute rabbit or human thromboplastin. Various dilutions of thromboplastin and calcium were added to plasma samples containing 3H-factor X, and the time course of factor X activation was determined. At a 1/250 dilution of rabbit brain thromboplastin, the rate of factor X activation in plasmas deficient in factor VIII or factor IX was 10% of the activation rate of normal plasma or of factor XI deficient plasma. Reconstitution of the deficient plasmas with factors VIII or IX, respectively, reconstituted normal factor X activation. Similar results were obtained when various dilutions of human thromboplastin replaced the rabbit thromboplastin. From these plasma experiments, it is inferred that the dilute thromboplastin-dependent activation of factor X requires factors VII, IX, and VIII. An alternative extrinsic pathway that involves factors IX and VIII may be the physiologic extrinsic pathway and hence help to explain the consistent clinical observations of bleeding diatheses in patients deficient in factors IX or VIII

Layered Downlink Precoding for C-RAN Systems with Full Dimensional MIMO

OpenAIRE

Kang, Jinkyu; Simeone, Osvaldo; Kang, Joonhyuk; Shamai, Shlomo

2015-01-01

The implementation of a Cloud Radio Access Network (C-RAN) with Full Dimensional (FD)-MIMO is faced with the challenge of controlling the fronthaul overhead for the transmission of baseband signals as the number of horizontal and vertical antennas grows larger. This work proposes to leverage the special low-rank structure of FD-MIMO channel, which is characterized by a time-invariant elevation component and a time-varying azimuth component, by means of a layered precoding approach, so as to r...

The production, purification and crystallization of a soluble form of the nonclassical MHC HLA-G: the essential role of cobalt

International Nuclear Information System (INIS)

Clements, Craig S.; Kjer-Nielsen, Lars; Kostenko, Lyudmila; McCluskey, James; Rossjohn, Jamie

2005-01-01

X-ray diffraction data were collected to 1.9 Å from crystals of HLA-G. Cobalt ions were found to be essential for the production of diffracting crystals. HLA-G is a nonclassical class I major histocompatibility complex (MHC) molecule that is primarily expressed at the foetal–maternal interface. Although the role of HLA-G has not been fully elucidated, current evidence suggests it protects the foetus from the maternal immune response. In this report, HLA-G (44 kDa) is characterized by expression in Escherichia coli. The inclusion bodies were refolded in complex with a peptide derived from histone H2A (RIIPRHLQL), purified and subsequently crystallized. Correct refolding was determined using two conformation-dependent antibodies. Cobalt ions were shown to be an essential ingredient for obtaining diffraction-quality crystals. The crystals, which diffracted to 1.9 Å resolution, belonged to space group P3 2 2 1 , with unit-cell parameters a = b = 77.15, c = 151.72 Å

Berberine regulates neurite outgrowth through AMPK-dependent pathways by lowering energy status

Energy Technology Data Exchange (ETDEWEB)

Lu, Jiaqi; Cao, Yuanzhao; Cheng, Kuoyuan; Xu, Bo; Wang, Tianchang; Yang, Qi; Yang, Qin [State Key Laboratory of Natural and Biomimetic Drugs, Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing (China); Feng, Xudong, E-mail: xudong.feng@childrens.harvard.edu [Department of Medicine, Children' s Hospital Boston, Harvard Medical School, 300 Longwood Ave, Boston, MA 02115 (United States); Xia, Qing, E-mail: xqing@hsc.pku.edu.cn [State Key Laboratory of Natural and Biomimetic Drugs, Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing (China)

2015-06-10

As a widely used anti-bacterial agent and a metabolic inhibitor as well as AMP-activated protein kinase (AMPK) activator, berberine (BBR) has been shown to cross the blood–brain barrier. Its efficacy has been investigated in various disease models of the central nervous system. Neurite outgrowth is critical for nervous system development and is a highly energy-dependent process regulated by AMPK-related pathways. In the present study, we aimed to investigate the effects of BBR on AMPK activation and neurite outgrowth in neurons. The neurite outgrowth of primary rat cortical neurons at different stages of polarization was monitored after exposure of BBR. Intracellular energy level, AMPK activation and polarity-related pathways were also inspected. The results showed that BBR suppressed neurite outgrowth and affected cytoskeleton stability in the early stages of neuronal polarization, which was mediated by lowered energy status and AMPK activation. Liver kinase B1 and PI3K–Akt–GSK3β signaling pathways were also involved. In addition, mitochondrial dysfunction and endoplasmic reticulum stress contributed to the lowered energy status induced by BBR. This study highlighted the knowledge of the complex activities of BBR in neurons and corroborated the significance of energy status during the neuronal polarization. - Highlights: • BBR inhibited neurite outgrowth in early stages of neuronal development. • Lowered neuronal energy status was induced by BBR treatment. • Neuronal energy stress induced by BBR activated AMPK-related pathways. • BBR induced mitochondrial dysfunction and endoplasmic reticulum stress.

Berberine regulates neurite outgrowth through AMPK-dependent pathways by lowering energy status

International Nuclear Information System (INIS)

Lu, Jiaqi; Cao, Yuanzhao; Cheng, Kuoyuan; Xu, Bo; Wang, Tianchang; Yang, Qi; Yang, Qin; Feng, Xudong; Xia, Qing

2015-01-01

As a widely used anti-bacterial agent and a metabolic inhibitor as well as AMP-activated protein kinase (AMPK) activator, berberine (BBR) has been shown to cross the blood–brain barrier. Its efficacy has been investigated in various disease models of the central nervous system. Neurite outgrowth is critical for nervous system development and is a highly energy-dependent process regulated by AMPK-related pathways. In the present study, we aimed to investigate the effects of BBR on AMPK activation and neurite outgrowth in neurons. The neurite outgrowth of primary rat cortical neurons at different stages of polarization was monitored after exposure of BBR. Intracellular energy level, AMPK activation and polarity-related pathways were also inspected. The results showed that BBR suppressed neurite outgrowth and affected cytoskeleton stability in the early stages of neuronal polarization, which was mediated by lowered energy status and AMPK activation. Liver kinase B1 and PI3K–Akt–GSK3β signaling pathways were also involved. In addition, mitochondrial dysfunction and endoplasmic reticulum stress contributed to the lowered energy status induced by BBR. This study highlighted the knowledge of the complex activities of BBR in neurons and corroborated the significance of energy status during the neuronal polarization. - Highlights: • BBR inhibited neurite outgrowth in early stages of neuronal development. • Lowered neuronal energy status was induced by BBR treatment. • Neuronal energy stress induced by BBR activated AMPK-related pathways. • BBR induced mitochondrial dysfunction and endoplasmic reticulum stress

Analysis of multiuser mixed RF/FSO relay networks for performance improvements in Cloud Computing-Based Radio Access Networks (CC-RANs)

Science.gov (United States)

Alimi, Isiaka A.; Monteiro, Paulo P.; Teixeira, António L.

2017-11-01

The key paths toward the fifth generation (5G) network requirements are towards centralized processing and small-cell densification systems that are implemented on the cloud computing-based radio access networks (CC-RANs). The increasing recognitions of the CC-RANs can be attributed to their valuable features regarding system performance optimization and cost-effectiveness. Nevertheless, realization of the stringent requirements of the fronthaul that connects the network elements is highly demanding. In this paper, considering the small-cell network architectures, we present multiuser mixed radio-frequency/free-space optical (RF/FSO) relay networks as feasible technologies for the alleviation of the stringent requirements in the CC-RANs. In this study, we use the end-to-end (e2e) outage probability, average symbol error probability (ASEP), and ergodic channel capacity as the performance metrics in our analysis. Simulation results show the suitability of deployment of mixed RF/FSO schemes in the real-life scenarios.

The generation of arbitrary order, non-classical, Gauss-type quadrature for transport applications

International Nuclear Information System (INIS)

Spence, Peter J.

2015-01-01

A method is presented, based upon the Stieltjes method (1884), for the determination of non-classical Gauss-type quadrature rules, and the associated sets of abscissae and weights. The method is then used to generate a number of quadrature sets, to arbitrary order, which are primarily aimed at deterministic transport calculations. The quadrature rules and sets detailed include arbitrary order reproductions of those presented by Abu-Shumays in [4,8] (known as the QR sets, but labelled QRA here), in addition to a number of new rules and associated sets; these are generated in a similar way, and we label them the QRS quadrature sets. The method presented here shifts the inherent difficulty (encountered by Abu-Shumays) associated with solving the non-linear moment equations, particular to the required quadrature rule, to one of the determination of non-classical weight functions and the subsequent calculation of various associated inner products. Once a quadrature rule has been written in a standard form, with an associated weight function having been identified, the calculation of the required inner products is achieved using specific variable transformations, in addition to the use of rapid, highly accurate quadrature suited to this purpose. The associated non-classical Gauss quadrature sets can then be determined, and this can be done to any order very rapidly. In this paper, instead of listing weights and abscissae for the different quadrature sets detailed (of which there are a number), the MATLAB code written to generate them is included as Appendix D. The accuracy and efficacy (in a transport setting) of the quadrature sets presented is not tested in this paper (although the accuracy of the QRA quadrature sets has been studied in [12,13]), but comparisons to tabulated results listed in [8] are made. When comparisons are made with one of the azimuthal QRA sets detailed in [8], the inherent difficulty in the method of generation, used there, becomes apparent

The generation of arbitrary order, non-classical, Gauss-type quadrature for transport applications

Energy Technology Data Exchange (ETDEWEB)

Spence, Peter J., E-mail: peter.spence@awe.co.uk

2015-09-01

A method is presented, based upon the Stieltjes method (1884), for the determination of non-classical Gauss-type quadrature rules, and the associated sets of abscissae and weights. The method is then used to generate a number of quadrature sets, to arbitrary order, which are primarily aimed at deterministic transport calculations. The quadrature rules and sets detailed include arbitrary order reproductions of those presented by Abu-Shumays in [4,8] (known as the QR sets, but labelled QRA here), in addition to a number of new rules and associated sets; these are generated in a similar way, and we label them the QRS quadrature sets. The method presented here shifts the inherent difficulty (encountered by Abu-Shumays) associated with solving the non-linear moment equations, particular to the required quadrature rule, to one of the determination of non-classical weight functions and the subsequent calculation of various associated inner products. Once a quadrature rule has been written in a standard form, with an associated weight function having been identified, the calculation of the required inner products is achieved using specific variable transformations, in addition to the use of rapid, highly accurate quadrature suited to this purpose. The associated non-classical Gauss quadrature sets can then be determined, and this can be done to any order very rapidly. In this paper, instead of listing weights and abscissae for the different quadrature sets detailed (of which there are a number), the MATLAB code written to generate them is included as Appendix D. The accuracy and efficacy (in a transport setting) of the quadrature sets presented is not tested in this paper (although the accuracy of the QRA quadrature sets has been studied in [12,13]), but comparisons to tabulated results listed in [8] are made. When comparisons are made with one of the azimuthal QRA sets detailed in [8], the inherent difficulty in the method of generation, used there, becomes apparent

Ofloxacin induces apoptosis in microencapsulated juvenile rabbit chondrocytes by caspase-8-dependent mitochondrial pathway

International Nuclear Information System (INIS)

Sheng Zhiguo; Cao Xiaojuan; Peng Shuangqing; Wang Changyong; Li Qianqian; Wang Yimei; Liu Mifeng

2008-01-01

Quinolones (QNs)-induced arthropathy is an important toxic effect in immature animals leading to restriction of their therapeutic use in pediatrics. However, the exact mechanism still remains unclear. Recently, we have demonstrated that ofloxacin, a typical QN, induces apoptosis of alginate microencapsulated juvenile rabbit joint chondrocytes by disturbing the β 1 integrin functions and inactivating the ERK/MAPK signaling pathway. In this study, we extend our initial observations to further elucidate the mechanism(s) of ofloxacin-induced apoptosis by utilizing specific caspase inhibitors. Pretreatment with both caspase-9-specific inhibitor zLEHD-fmk and caspase-8 inhibitor zIETD-fmk attenuated ofloxacin-induced apoptosis and activation of caspase-3 of chondrocyte in a concentration-dependent manner, as determined by fluorescent dye staining, enzyme activity assay and immunoblotting. Furthermore, the activation of caspase-9, -8 and -3 stimulated by ofloxacin was significantly inhibited in the presence of zIETD-fmk while pretreatment with zLEHD-fmk only blocked the activation of caspase-9 and -3. Ofloxacin also stimulated a concentration-dependent translocation of cytochrome c from mitochondria into the cytosol and a decrease of mitochondrial transmembrane potential, which was completely inhibited by zIETD-fmk. In addition, ofloxacin was found to increase the level of Bax, tBid, p53 in a concentration- and time-dependent manner. Taken together, The current results indicate that the caspase-8-dependent mitochondrial pathway is primarily involved in the ofloxacin-induced apoptosis of microencapsulated juvenile rabbit joint chondrocytes

Rodent Models of Non-classical Progesterone Action Regulating Ovulation

Directory of Open Access Journals (Sweden)

Melinda A. Mittelman-Smith

2017-07-01

Full Text Available It is becoming clear that steroid hormones act not only by binding to nuclear receptors that associate with specific response elements in the nucleus but also by binding to receptors on the cell membrane. In this newly discovered manner, steroid hormones can initiate intracellular signaling cascades which elicit rapid effects such as release of internal calcium stores and activation of kinases. We have learned much about the translocation and signaling of steroid hormone receptors from investigations into estrogen receptor α, which can be trafficked to, and signal from, the cell membrane. It is now clear that progesterone (P4 can also elicit effects that cannot be exclusively explained by transcriptional changes. Similar to E2 and its receptors, P4 can initiate signaling at the cell membrane, both through progesterone receptor and via a host of newly discovered membrane receptors (e.g., membrane progesterone receptors, progesterone receptor membrane components. This review discusses the parallels between neurotransmitter-like E2 action and the more recently investigated non-classical P4 signaling, in the context of reproductive behaviors in the rodent.

OTN Transport of Baseband Radio Serial Protocols in C-RAN Architecture for Mobile Network Applications

DEFF Research Database (Denmark)

Checko, Aleksandra; Kardaras, Georgios; Lanzani, Christian Fabio Alessandro

This white paper presents a proof of concept implementation of digital baseband radio data transport over Optical Transport Network (OTN) compliant to 3GPP Long Term Evolution – Advanced (LTE-A) standard enabling Cloud Radio Access Network (C-RAN) architecture. The transport between the baseband ...

Erythrocyte signal transduction pathways, their oxygenation dependence and functional significance.

Science.gov (United States)

Barvitenko, Nadezhda N; Adragna, Norma C; Weber, Roy E

2005-01-01

Erythrocytes play a key role in human and vertebrate metabolism. Tissue O2 supply is regulated by both hemoglobin (Hb)-O2 affinity and erythrocyte rheology, a key determinant of tissue perfusion. Oxygenation-deoxygenation transitions of Hb may lead to re-organization of the cytoskeleton and signalling pathways activation/deactivation in an O2-dependent manner. Deoxygenated Hb binds to the cytoplasmic domain of the anion exchanger band 3, which is anchored to the cytoskeleton, and is considered a major mechanism underlying the oxygenation-dependence of several erythrocyte functions. This work discusses the multiple modes of Hb-cytoskeleton interactions. In addition, it reviews the effects of Mg2+, 2,3-diphosphoglycerate, NO, shear stress and Ca2+, all factors accompanying the oxygenation-deoxygenation cycle in circulating red cells. Due to the extensive literature on the subject, the data discussed here, pertain mainly to human erythrocytes whose O2 affinity is modulated by 2,3-diphosphoglycerate, ectothermic vertebrate erythrocytes that use ATP, and to bird erythrocytes that use inositol pentaphosphate. Copyright 2005 S. Karger AG, Basel.

Algorithmes de couplage RANS et ecoulement potentiel

Science.gov (United States)

Gallay, Sylvain

-decrochage. L'algorithme de couplage a ete compare a des donnees de plus haute fidelite sur des configurations issues de la litterature. Un modele de fuselage base sur des relations empiriques et des simulations RANS a ete teste et valide. Les coefficients de portance, de trainee et de moment de tangage ainsi que les coefficients de pression extraits le long de l'envergure ont montre un bon accord avec les donnees de soufflerie et les modeles RANS pour des configurations transsoniques. Une configuration a geometrie hypersustentatoire a permis d'etudier la modelisation des surfaces hypersustentees de la methode d'ecoulement potentiel, demontrant que la cambrure peut etre prise en compte uniquement dans les donnees visqueuses.

4SC-202 activates ASK1-dependent mitochondrial apoptosis pathway to inhibit hepatocellular carcinoma cells

International Nuclear Information System (INIS)

Fu, Meili; Wan, Fuqiang; Li, Zhengling; Zhang, Fenghua

2016-01-01

The aim of the present study is to investigate the potential anti-hepatocellular carcinoma (HCC) cell activity by 4SC-202, a novel class I HDAC inhibitor (HDACi). The associated signaling mechanisms were also analyzed. We showed that 4SC-202 treatment induced potent cytotoxic and proliferation–inhibitory activities against established HCC cell lines (HepG2, HepB3, SMMC-7721) and patient-derived primary HCC cells. Further, adding 4SC-202 in HCC cells activated mitochondrial apoptosis pathway, which was evidenced by mitochondrial permeability transition pore (mPTP) opening, cytochrome C cytosol release and caspase-3/-9 activation. Inhibition of this apoptosis pathway, by caspase-3/-9 inhibitors, mPTP blockers, or by shRNA-mediated knockdown of cyclophilin-D (Cyp-D, a key component of mPTP), significantly attenuated 4SC-202-induced HCC cell death and apoptosis. Reversely, over-expression of Cyp-D enhanced 4SC-202's sensitivity in HCC cells. Further studies showed that 4SC-202 induced apoptosis signal-regulating kinase 1 (ASK1) activation, causing it translocation to mitochondria and physical association with Cyp-D. This mitochondrial ASK1-Cyp-D complexation appeared required for mediating 4SC-202-induced apoptosis activation. ASK1 stable knockdown by targeted-shRNAs largely inhibited 4SC-202-induced mPTP opening, cytochrome C release, and following HCC cell apoptotic death. Together, we suggest that 4SC-202 activates ASK1-dependent mitochondrial apoptosis pathway to potently inhibit human HCC cells. - Highlights: • 4SC-202 exerts potent anti-proliferative and cytotoxic activity against established/primary HCC cells. • SC-202-induced anti-HCC cell activity relies on caspase-dependent apoptosis activation. • 4SC-202 activates Cyp-D-dependent mitochondrial apoptosis pathway in HCC cells. • 4SC-202 activates ASK1 in HCC cells, causing it translocation to mitochondria. • Mitochondrial ASK1-Cyp-D complexation mediates 4SC-202's activity in HCC cells.

4SC-202 activates ASK1-dependent mitochondrial apoptosis pathway to inhibit hepatocellular carcinoma cells

Energy Technology Data Exchange (ETDEWEB)

Fu, Meili, E-mail: fumeilidrlinyi@tom.com [Department of Infectious Disease, Linyi People' s Hospital, Linyi 276000 (China); Wan, Fuqiang [Department of Head and Neck Surgery, Linyi Tumor Hospital, Linyi 276000 (China); Li, Zhengling [Department of Nursing, Tengzhou Central People' s Hospital, Tengzhou 277500 (China); Zhang, Fenghua [Department of Operating Room, Linyi People' s Hospital, Linyi 276000 (China)

2016-03-04

The aim of the present study is to investigate the potential anti-hepatocellular carcinoma (HCC) cell activity by 4SC-202, a novel class I HDAC inhibitor (HDACi). The associated signaling mechanisms were also analyzed. We showed that 4SC-202 treatment induced potent cytotoxic and proliferation–inhibitory activities against established HCC cell lines (HepG2, HepB3, SMMC-7721) and patient-derived primary HCC cells. Further, adding 4SC-202 in HCC cells activated mitochondrial apoptosis pathway, which was evidenced by mitochondrial permeability transition pore (mPTP) opening, cytochrome C cytosol release and caspase-3/-9 activation. Inhibition of this apoptosis pathway, by caspase-3/-9 inhibitors, mPTP blockers, or by shRNA-mediated knockdown of cyclophilin-D (Cyp-D, a key component of mPTP), significantly attenuated 4SC-202-induced HCC cell death and apoptosis. Reversely, over-expression of Cyp-D enhanced 4SC-202's sensitivity in HCC cells. Further studies showed that 4SC-202 induced apoptosis signal-regulating kinase 1 (ASK1) activation, causing it translocation to mitochondria and physical association with Cyp-D. This mitochondrial ASK1-Cyp-D complexation appeared required for mediating 4SC-202-induced apoptosis activation. ASK1 stable knockdown by targeted-shRNAs largely inhibited 4SC-202-induced mPTP opening, cytochrome C release, and following HCC cell apoptotic death. Together, we suggest that 4SC-202 activates ASK1-dependent mitochondrial apoptosis pathway to potently inhibit human HCC cells. - Highlights: • 4SC-202 exerts potent anti-proliferative and cytotoxic activity against established/primary HCC cells. • SC-202-induced anti-HCC cell activity relies on caspase-dependent apoptosis activation. • 4SC-202 activates Cyp-D-dependent mitochondrial apoptosis pathway in HCC cells. • 4SC-202 activates ASK1 in HCC cells, causing it translocation to mitochondria. • Mitochondrial ASK1-Cyp-D complexation mediates 4SC-202's activity in HCC cells.

Hybrid RANS/LES method for high Reynolds numbers, applied to atmospheric flow over complex terrain

DEFF Research Database (Denmark)

Bechmann, Andreas; Sørensen, Niels N.; Johansen, Jeppe

2007-01-01

  The use of Large-Eddy Simulation (LES) to predict wall-bounded flows has presently been limited to low Reynolds number flows. Since the number of computational grid points required to resolve the near-wall turbulent structures increase rapidly with Reynolds number, LES has been unattainable...... for flows at high Reynolds numbers. To reduce the computational cost of traditional LES a hybrid method is proposed in which the near-wall eddies are modelled in a Reynolds-averaged sense. Close to walls the flow is treated with the RANS-equations and this layer act as wall model for the outer flow handled...... by LES. The wellknown high Reynolds number two-equation k - ǫ turbulence model is used in the RANS layer and the model automatically switches to a two-equation k - ǫ subgrid-scale stress model in the LES region. The approach can be used for flow over rough walls. To demonstrate the ability...

MAPK pathway activation by chronic lead-exposure increases vascular reactivity through oxidative stress/cyclooxygenase-2-dependent pathways

Energy Technology Data Exchange (ETDEWEB)

Simões, Maylla Ronacher, E-mail: yllars@hotmail.com [Dept. of Physiological Sciences, Federal University of Espirito Santo, Vitória, ES CEP 29040-091 (Brazil); Department of Pharmacology, Universidad Autonoma de Madrid, Instituto de Investigación Hospital Universitario La Paz (IdiPAZ), Madrid (Spain); Aguado, Andrea [Department of Pharmacology, Universidad Autonoma de Madrid, Instituto de Investigación Hospital Universitario La Paz (IdiPAZ), Madrid (Spain); Fiorim, Jonaína; Silveira, Edna Aparecida; Azevedo, Bruna Fernandes; Toscano, Cindy Medice [Dept. of Physiological Sciences, Federal University of Espirito Santo, Vitória, ES CEP 29040-091 (Brazil); Zhenyukh, Olha; Briones, Ana María [Department of Pharmacology, Universidad Autonoma de Madrid, Instituto de Investigación Hospital Universitario La Paz (IdiPAZ), Madrid (Spain); Alonso, María Jesús [Dept. of Biochemistry, Physiology and Molecular Genetics, Universidad Rey Juan Carlos, Alcorcón (Spain); Vassallo, Dalton Valentim [Dept. of Physiological Sciences, Federal University of Espirito Santo, Vitória, ES CEP 29040-091 (Brazil); Health Science Center of Vitória-EMESCAM, Vitória, ES CEP 29045-402 (Brazil); Salaices, Mercedes, E-mail: mercedes.salaices@uam.es [Department of Pharmacology, Universidad Autonoma de Madrid, Instituto de Investigación Hospital Universitario La Paz (IdiPAZ), Madrid (Spain)

2015-03-01

Chronic exposure to low lead concentration produces hypertension; however, the underlying mechanisms remain unclear. We analyzed the role of oxidative stress, cyclooxygenase-2-dependent pathways and MAPK in the vascular alterations induced by chronic lead exposure. Aortas from lead-treated Wistar rats (1st dose: 10 μg/100 g; subsequent doses: 0.125 μg/100 g, intramuscular, 30 days) and cultured aortic vascular smooth muscle cells (VSMCs) from Sprague Dawley rats stimulated with lead (20 μg/dL) were used. Lead blood levels of treated rats attained 21.7 ± 2.38 μg/dL. Lead exposure increased systolic blood pressure and aortic ring contractile response to phenylephrine, reduced acetylcholine-induced relaxation and did not affect sodium nitroprusside relaxation. Endothelium removal and L-NAME left-shifted the response to phenylephrine more in untreated than in lead-treated rats. Apocynin and indomethacin decreased more the response to phenylephrine in treated than in untreated rats. Aortic protein expression of gp91(phox), Cu/Zn-SOD, Mn-SOD and COX-2 increased after lead exposure. In cultured VSMCs lead 1) increased superoxide anion production, NADPH oxidase activity and gene and/or protein levels of NOX-1, NOX-4, Mn-SOD, EC-SOD and COX-2 and 2) activated ERK1/2 and p38 MAPK. Both antioxidants and COX-2 inhibitors normalized superoxide anion production, NADPH oxidase activity and mRNA levels of NOX-1, NOX-4 and COX-2. Blockade of the ERK1/2 and p38 signaling pathways abolished lead-induced NOX-1, NOX-4 and COX-2 expression. Results show that lead activation of the MAPK signaling pathways activates inflammatory proteins such as NADPH oxidase and COX-2, suggesting a reciprocal interplay and contribution to vascular dysfunction as an underlying mechanisms for lead-induced hypertension. - Highlights: • Lead-exposure increases oxidative stress, COX-2 expression and vascular reactivity. • Lead exposure activates MAPK signaling pathway. • ROS and COX-2 activation by

Enhancing LTE with Cloud-RAN and Load-Controlled Parasitic Antenna Arrays

DEFF Research Database (Denmark)

Artuso, Matteo; Boviz, Dora; Checko, Aleksandra

2016-01-01

Cloud radio access network systems, consisting of remote radio heads densely distributed in a coverage area and connected by optical fibers to a cloud infrastructure with large computational capabilities, have the potential to meet the ambitious objectives of next generation mobile networks. Actual...... presented for the fronthaul enables flexibility and elasticity in resource allocation to support BS virtualization. A layered design of information control for the proposed end-to-end solution is presented. The feasibility and effectiveness of such an LCPAA-enabled C-RAN system setup has been validated...

Dissecting Bacterial Cell Wall Entry and Signaling in Eukaryotic Cells: an Actin-Dependent Pathway Parallels Platelet-Activating Factor Receptor-Mediated Endocytosis.

Science.gov (United States)

Loh, Lip Nam; Gao, Geli; Tuomanen, Elaine I

2017-01-03

The Gram-positive bacterial cell wall (CW) peptidoglycan-teichoic acid complex is released into the host environment during bacterial metabolism or death. It is a highly inflammatory Toll-like receptor 2 (TLR2) ligand, and previous in vivo studies have demonstrated its ability to recapitulate pathological features of pneumonia and meningitis. We report that an actin-dependent pathway is involved in the internalization of the CW by epithelial and endothelial cells, in addition to the previously described platelet-activating factor receptor (PAFr)-dependent uptake pathway. Unlike the PAFr-dependent pathway, which is mediated by clathrin and dynamin and does not lead to signaling, the alternative pathway is sensitive to 5-(N-ethyl-N-isopropyl) amiloride (EIPA) and engenders Rac1, Cdc42, and phosphatidylinositol 3-kinase (PI3K) signaling. Upon internalization by this macropinocytosis-like pathway, CW is trafficked to lysosomes. Intracellular CW trafficking is more complex than previously recognized and suggests multiple points of interaction with and without innate immune signaling. Streptococcus pneumoniae is a major human pathogen infecting the respiratory tract and brain. It is an established model organism for understanding how infection injures the host. During infection or bacterial growth, bacteria shed their cell wall (CW) into the host environment and trigger inflammation. A previous study has shown that CW enters and crosses cell barriers by interacting with a receptor on the surfaces of host cells, termed platelet-activating factor receptor (PAFr). In the present study, by using cells that are depleted of PAFr, we identified a second pathway with features of macropinocytosis, which is a receptor-independent fluid uptake mechanism by cells. Each pathway contributes approximately the same amount of cell wall trafficking, but the PAFr pathway is silent, while the new pathway appears to contribute to the host inflammatory response to CW insult. Copyright © 2017

A Priori Analysis of a Compressible Flamelet Model using RANS Data for a Dual-Mode Scramjet Combustor

Science.gov (United States)

Quinlan, Jesse R.; Drozda, Tomasz G.; McDaniel, James C.; Lacaze, Guilhem; Oefelein, Joseph

2015-01-01

In an effort to make large eddy simulation of hydrocarbon-fueled scramjet combustors more computationally accessible using realistic chemical reaction mechanisms, a compressible flamelet/progress variable (FPV) model was proposed that extends current FPV model formulations to high-speed, compressible flows. Development of this model relied on observations garnered from an a priori analysis of the Reynolds-Averaged Navier-Stokes (RANS) data obtained for the Hypersonic International Flight Research and Experimentation (HI-FiRE) dual-mode scramjet combustor. The RANS data were obtained using a reduced chemical mechanism for the combustion of a JP-7 surrogate and were validated using avail- able experimental data. These RANS data were then post-processed to obtain, in an a priori fashion, the scalar fields corresponding to an FPV-based modeling approach. In the current work, in addition to the proposed compressible flamelet model, a standard incompressible FPV model was also considered. Several candidate progress variables were investigated for their ability to recover static temperature and major and minor product species. The effects of pressure and temperature on the tabulated progress variable source term were characterized, and model coupling terms embedded in the Reynolds- averaged Navier-Stokes equations were studied. Finally, results for the novel compressible flamelet/progress variable model were presented to demonstrate the improvement attained by modeling the effects of pressure and flamelet boundary conditions on the combustion.

RNAi screen reveals an Abl kinase-dependent host cell pathway involved in Pseudomonas aeruginosa internalization.

Directory of Open Access Journals (Sweden)

Julia F Pielage

2008-03-01

Full Text Available Internalization of the pathogenic bacterium Pseudomonas aeruginosa by non-phagocytic cells is promoted by rearrangements of the actin cytoskeleton, but the host pathways usurped by this bacterium are not clearly understood. We used RNAi-mediated gene inactivation of approximately 80 genes known to regulate the actin cytoskeleton in Drosophila S2 cells to identify host molecules essential for entry of P. aeruginosa. This work revealed Abl tyrosine kinase, the adaptor protein Crk, the small GTPases Rac1 and Cdc42, and p21-activated kinase as components of a host signaling pathway that leads to internalization of P. aeruginosa. Using a variety of complementary approaches, we validated the role of this pathway in mammalian cells. Remarkably, ExoS and ExoT, type III secreted toxins of P. aeruginosa, target this pathway by interfering with GTPase function and, in the case of ExoT, by abrogating P. aeruginosa-induced Abl-dependent Crk phosphorylation. Altogether, this work reveals that P. aeruginosa utilizes the Abl pathway for entering host cells and reveals unexpected complexity by which the P. aeruginosa type III secretion system modulates this internalization pathway. Our results furthermore demonstrate the applicability of using RNAi screens to identify host signaling cascades usurped by microbial pathogens that may be potential targets for novel therapies directed against treatment of antibiotic-resistant infections.

İran Mitolojisinin İslam Devrimindeki Rolü & Humeyni ve Şah’ın Söylemlerinin Analizi

Directory of Open Access Journals (Sweden)

Fatih TİRYAKİ

2015-09-01

Full Text Available İran tarihinde köklü değişimler meydana getiren İran İslam devrimi birçok farklı açıdan analiz edilmiş olsa da bu analizlerin pek azı devrimi mitolojik çerçeve ile temellendirmektedir. Böylesine köklü bir devletin geçmişle olan bağlarının her daim canlı olduğu gerçeğini varsayar isek devrim sürecinde de halkın bilinçaltındaki mitolojik inanışların önemli bir payı olduğunu söylemek mümkündür. Bu bilgiler ışığında biz bu çalışmamızda İran mitolojisinin devrime olan etkilerini ve hem Şah’ın hem de Humeyni’nin bu dönemdeki söylemlerini mitolojik bir perspektiften değerlendireceğiz. Bunu yaparken de 1953 Musaddık devrimini milat olarak kabul edip bu tarihten devrime kadar geçen kırılma noktalarını kronolojik bir sıra ile anakronizme kaçmadan incelerken olayları son tahlilde mitoloji ile ilişkilendireceğiz. Sonuç bölümünde ise devrim ile esasında çok fazla şeyin değişmediğini, değişenin yalnızca meşruiyetini ve İran halkının baba figürü olma özelliğini kaybeden Şah’ın yerine halkçı ve sözde fundemantalist söylemleri ile halkı derinden etkileyen yeni baba figürü Humeyni’nin geldiği tespitlerinde bulunacağız

RANS modeling for particle transport and deposition in turbulent duct flows: Near wall model uncertainties

International Nuclear Information System (INIS)

Jayaraju, S.T.; Sathiah, P.; Roelofs, F.; Dehbi, A.

2015-01-01

Highlights: • Near-wall modeling uncertainties in the RANS particle transport and deposition are addressed in a turbulent duct flow. • Discrete Random Walk (DRW) model and Continuous Random Walk (CRW) model performances are tested. • Several near-wall anisotropic model accuracy is assessed. • Numerous sensitivity studies are performed to recommend a robust, well-validated near-wall model for accurate particle deposition predictions. - Abstract: Dust accumulation in the primary system of a (V)HTR is identified as one of the foremost concerns during a potential accident. Several numerical efforts have focused on the use of RANS methodology to better understand the complex phenomena of fluid–particle interaction at various flow conditions. In the present work, several uncertainties relating to the near-wall modeling of particle transport and deposition are addressed for the RANS approach. The validation analyses are performed in a fully developed turbulent duct flow setup. A standard k − ε turbulence model with enhanced wall treatment is used for modeling the turbulence. For the Lagrangian phase, the performance of a continuous random walk (CRW) model and a discrete random walk (DRW) model for the particle transport and deposition are assessed. For wall bounded flows, it is generally seen that accounting for near wall anisotropy is important to accurately predict particle deposition. The various near-wall correlations available in the literature are either derived from the DNS data or from the experimental data. A thorough investigation into various near-wall correlations and their applicability for accurate particle deposition predictions are assessed. The main outcome of the present work is a well validated turbulence model with optimal near-wall modeling which provides realistic particle deposition predictions

Multi-crack imaging using nonclassical nonlinear acoustic method

Science.gov (United States)

Zhang, Lue; Zhang, Ying; Liu, Xiao-Zhou; Gong, Xiu-Fen

2014-10-01

Solid materials with cracks exhibit the nonclassical nonlinear acoustical behavior. The micro-defects in solid materials can be detected by nonlinear elastic wave spectroscopy (NEWS) method with a time-reversal (TR) mirror. While defects lie in viscoelastic solid material with different distances from one another, the nonlinear and hysteretic stress—strain relation is established with Preisach—Mayergoyz (PM) model in crack zone. Pulse inversion (PI) and TR methods are used in numerical simulation and defect locations can be determined from images obtained by the maximum value. Since false-positive defects might appear and degrade the imaging when the defects are located quite closely, the maximum value imaging with a time window is introduced to analyze how defects affect each other and how the fake one occurs. Furthermore, NEWS-TR-NEWS method is put forward to improve NEWS-TR scheme, with another forward propagation (NEWS) added to the existing phases (NEWS and TR). In the added phase, scanner locations are determined by locations of all defects imaged in previous phases, so that whether an imaged defect is real can be deduced. NEWS-TR-NEWS method is proved to be effective to distinguish real defects from the false-positive ones. Moreover, it is also helpful to detect the crack that is weaker than others during imaging procedure.

In vitro expression of Sec-dependent pathway and type 4B secretion system in Piscirickettsia salmonis.

Science.gov (United States)

Cortés, Marcos; Sánchez, Patricio; Ruiz, Pamela; Haro, Ronie; Sáez, Jerson; Sánchez, Fabián; Hernández, Mauricio; Oliver, Cristian; Yáñez, Alejandro J

2017-09-01

Piscirickettsia salmonis is an intracellular bacterium and the causative agent of Piscirickettsiosis, a disease responsible for considerable mortalities in the Chilean salmon farming industry. Currently, P. salmonis protein translocation across the membrane and the mechanisms by which virulence factors are delivered to host cells are poorly understood. However, it is known that Gram-negative bacteria possess several mechanisms that transport proteins to the periplasmic and extracellular compartments. The aim of this study was to evaluate the expressional changes of several genes in the P. salmonis Sec-dependent pathway and type 4B secretion system during in vitro infection. Genes homologous and the main proteins belonging to Sec-dependent pathway and Type 4 Dot/Icm secretion system were found in the genome and proteome of P. salmonis AUSTRAL-005 strain. Additionally, several genes of these protein transport mechanisms were overexpressed during in vitro P. salmonis infection in SHK-1 cell line. The obtained data indicate that the Sec-dependent pathway and Type 4B secretion system are biologically active during P. salmonis infection. These mechanisms could contribute to the recycling of proteins into the inner and outer bacterial membrane and in translocate virulence factors to infected cell, which would favor the structural integrity and virulence of this bacterium. Copyright © 2017 Elsevier Ltd. All rights reserved.

Behavior of thin-walled beams made of advanced composite materials and incorporating non-classical effects

Science.gov (United States)

Librescu, Liviu; Song, Ohseop

1991-11-01

Several results concerning the refined theory of thin-walled beams of arbitrary closed cross-section incorporating nonclassical effects are presented. These effects are related both with the exotic properties characterizing the advanced composite material structures and the nonuniform torsional model. A special case of the general equations is used to study several problems of cantilevered thin-walled beams and to assess the influence of the incorporated effects. The results presented in this paper could be useful toward a more rational design of aeronautical or aerospace constructions, as well as of helicopter or tilt rotor blades constructed of advanced composite materials.

Universality of Nonclassical Nonlinearity Applications to Non-Destructive Evaluations and Ultrasonic

CERN Document Server

Delsanto, Pier Paolo

2006-01-01

This book comes as a result of the research work developed in the framework of two international projects: the European Science Foundation supported program NATEMIS (Nonlinear Acoustic Techniques for Micro-Scale Damage Diagnostics) and a Los Alamos-based international network. The main topics of both the programs and the book cover the phenomenology, theory and applications of Nonclassical Nonlinearity (NCNL). NCNL techniques have been found in recent years to be extremely powerful (up to 1000 times more than the corresponding linear techniques) in a wide range of applications, including Material Characterization, Ultrasonics, Geophysics and Maintenance and Restoration of artifacts. These techniques are being adopted as the main inspection and research tool in another European program: AERONEWS (Health monitoring of aircraft by nonlinear elastic wave propagation). In the future, the proposed Universality of NCNL is expected to extend the range of applications to numerous other fields and scientific discipline...

Contemporary commercial music (CCM) survey: who's teaching what in nonclassical music.

Science.gov (United States)

LoVetri, Jeannette L; Weekly, Edrie Means

2003-06-01

Currently, there is an increasing interest in and demand for training in a wide variety of nonclassical music--contemporary commercial music (CCM)--and most particularly for music theater. A survey of singing teachers was completed to elucidate their training, education, and experience with and methods of teaching CCM. Teachers were at colleges, universities, and conservatories as well as in private studios, both nationally and in several foreign countries. A substantial percentage of those teaching CCM had neither formal education in teaching it nor professional experience. Many of the respondents indicated conflict between classical and CCM styles. Respondents were generally familiar with voice science and voice medicine as well as certain CCM terminology. Teachers expressed an interest in obtaining more information, with an emphasis on healthy vocal production. These results are discussed, as well as implications for the singing teacher who desires specific training to teach CCM.

Computing the flow past Vortex Generators: Comparison between RANS Simulations and Experiments

DEFF Research Database (Denmark)

Manolesos, M.; Sørensen, Niels N.; Troldborg, Niels

2016-01-01

The flow around a wind turbine airfoil equipped with Vortex Generators (VGs) is examined. Predictions from three different Reynolds Averaged Navier Stokes (RANS) solvers with two different turbulence models and two different VG modelling approaches are compared between them and with experimental ...... data. The best results are obtained with the more expensive fully resolved VG approach. The cost efficient BAY model can also provide acceptable results, if grid related numerical diffusion is minimized and only force coefficient polars are considered....

Human cerebral venous outflow pathway depends on posture and central venous pressure

Science.gov (United States)

Gisolf, J; van Lieshout, J J; van Heusden, K; Pott, F; Stok, W J; Karemaker, J M

2004-01-01

Internal jugular veins are the major cerebral venous outflow pathway in supine humans. In upright humans the positioning of these veins above heart level causes them to collapse. An alternative cerebral outflow pathway is the vertebral venous plexus. We set out to determine the effect of posture and central venous pressure (CVP) on the distribution of cerebral outflow over the internal jugular veins and the vertebral plexus, using a mathematical model. Input to the model was a data set of beat-to-beat cerebral blood flow velocity and CVP measurements in 10 healthy subjects, during baseline rest and a Valsalva manoeuvre in the supine and standing position. The model, consisting of 2 jugular veins, each a chain of 10 units containing nonlinear resistances and capacitors, and a vertebral plexus containing a resistance, showed blood flow mainly through the internal jugular veins in the supine position, but mainly through the vertebral plexus in the upright position. A Valsalva manoeuvre while standing completely re-opened the jugular veins. Results of ultrasound imaging of the right internal jugular vein cross-sectional area at the level of the laryngeal prominence in six healthy subjects, before and during a Valsalva manoeuvre in both body positions, correlate highly with model simulation of the jugular cross-sectional area (R2 = 0.97). The results suggest that the cerebral venous flow distribution depends on posture and CVP: in supine humans the internal jugular veins are the primary pathway. The internal jugular veins are collapsed in the standing position and blood is shunted to an alternative venous pathway, but a marked increase in CVP while standing completely re-opens the jugular veins. PMID:15284348

Steady state RANS simulations of temperature fluctuations in single phase turbulent mixing

International Nuclear Information System (INIS)

Kickhofel, J.; Fokken, J.; Kapulla, R.; Prasser, H. M.

2012-01-01

Single phase turbulent mixing in nuclear power plant circuits where a strong temperature gradient is present is known to precipitate pipe failure due to thermal fatigue. Experiments in a square mixing channel offer the opportunity to study the phenomenon under simple and easily reproducible boundary conditions. Measurements of this kind have been performed extensively at the Paul Scherrer Inst. in Switzerland with a high density of instrumentation in the Generic Mixing Experiment (GEMIX). As a fundamental mixing phenomena study closely related to the thermal fatigue problem, the experimental results from GEMIX are valuable for the validation of CFD codes striving to accurately simulate both the temperature and velocity fields in single phase turbulent mixing. In the experiments two iso-kinetic streams meet at a shallow angle of 3 degrees and mix in a straight channel of square cross-section under various degrees of density, temperature, and viscosity stratification over a range of Reynolds numbers ranging from 5*10 3 to 1*10 5 . Conductivity measurements, using wire-mesh and wall sensors, as well as optical measurements, using particle image velocimetry, were conducted with high temporal and spatial resolutions (up to 2.5 kHz and 1 mm in the case of the wire mesh sensor) in the mixing zone, downstream of a splitter plate. The present paper communicates the results of RANS modeling of selected GEMIX tests. Steady-state CFD calculations using a RANS turbulence model represent an inexpensive method for analyzing large and complex components in commercial nuclear reactors, such as the downcomer and reactor pressure vessel heads. Crucial to real world applicability, however, is the ability to model turbulent heat fluctuations in the flow; the Turbulent Heat Flux Transport model developed by ANSYS CFX is capable, by implementation of a transport equation for turbulent heat fluxes, of readily modeling these values. Furthermore, the closure of the turbulent heat flux

Membrane estrogen receptors - is it an alternative way of estrogen action?

Science.gov (United States)

Soltysik, K; Czekaj, P

2013-04-01

The functions of estrogens are relatively well known, however the molecular mechanism of their action is not clear. The classical pathway of estrogen action is dependent on ERα and ERβ which act as transcription factors. The effects of this pathway occur within hours or days. In addition, so-called, non-classical mechanism of steroid action dependent on membrane estrogen receptors (mER) was described. In this mechanism the effects of estrogen action are observed in a much shorter time. Here we review the structure and cellular localization of mER, molecular basis of non-classical mER action, physiological role of mER as well as implications of mER action for cancer biology. Finally, some concerns about the new estrogen receptor - GPER and candidates for estrogen receptors - ER-X and ERx, are briefly discussed. It seems that mER is a complex containing signal proteins (signalosome), as IGF receptor, EGF receptor, Ras protein, adaptor protein Shc, non-receptor kinase c-Src and PI-3K, what rationalizes production of second messengers. Some features of membrane receptors are almost identical if compared to nuclear receptors. Probably, membrane and nuclear estrogen receptors are not separate units, but rather the components of a complex mechanism in which they both cooperate with each other. We conclude that the image of the estrogen receptor as a simple transcription factor is a far-reaching simplification. A better understanding of the mechanisms of estrogen action will help us to design more effective drugs affecting signal pathways depending on both membrane and nuclear receptors.

A fluorescent glycolipid-binding peptide probe traces cholesterol dependent microdomain-derived trafficking pathways.

Directory of Open Access Journals (Sweden)

Steffen Steinert

Full Text Available BACKGROUND: The uptake and intracellular trafficking of sphingolipids, which self-associate into plasma membrane microdomains, is associated with many pathological conditions, including viral and toxin infection, lipid storage disease, and neurodegenerative disease. However, the means available to label the trafficking pathways of sphingolipids in live cells are extremely limited. In order to address this problem, we have developed an exogenous, non-toxic probe consisting of a 25-amino acid sphingolipid binding domain, the SBD, derived from the amyloid peptide Abeta, and conjugated by a neutral linker with an organic fluorophore. The current work presents the characterization of the sphingolipid binding and live cell trafficking of this novel probe, the SBD peptide. SBD was the name given to a motif originally recognized by Fantini et al in a number of glycolipid-associated proteins, and was proposed to interact with sphingolipids in membrane microdomains. METHODOLOGY/PRINCIPAL FINDINGS: In accordance with Fantini's model, optimal SBD binding to membranes depends on the presence of sphingolipids and cholesterol. In synthetic membrane binding assays, SBD interacts preferentially with raft-like lipid mixtures containing sphingomyelin, cholesterol, and complex gangliosides in a pH-dependent manner, but is less glycolipid-specific than Cholera toxin B (CtxB. Using quantitative time-course colocalization in live cells, we show that the uptake and intracellular trafficking route of SBD is unlike that of either the non-raft marker Transferrin or the raft markers CtxB and Flotillin2-GFP. However, SBD traverses an endolysosomal route that partially intersects with raft-associated pathways, with a major portion being diverted at a late time point to rab11-positive recycling endosomes. Trafficking of SBD to acidified compartments is strongly disrupted by cholesterol perturbations, consistent with the regulation of sphingolipid trafficking by cholesterol

Stochastic Modeling of the Clathrin-dependent and -independent Endocytic Pathways

Science.gov (United States)

Deng, Hua; Dutta, Prashanta; Liu, Jin

2017-11-01

Endocytosis is one of the important processes that bioparticles use to enter the cells. During endocytosis the membrane-bound vesicles are formed by the invagination of plasma membrane as a result of interactions among many proteins and cytoskeletons. The clathrin-mediated endocytosis is one of the most significant form of endocytosis, where the dynamic assembly of clathrin-coated pits play a critical role. While herpes simplex virus-1 has recently shown to infect cell by a novel phagocytosis-like endocytic pathway where actin polymerization may facilitate the viral entry. In this work, we propose a stochastic model for both clathrin-dependent and -independent endocytic pathways based on Monte Carlo simulations. The important roles of clathrin coating and actin cytoskeleton as well as the impact of other biological parameters are studied. Our preliminary results indicate that there exist an intermediate particle size and ligand density that maximize the internalization efficiency. Below a critical size or surface ligand density, it is difficult for the entry of a single particle, which means clustering may needed for more efficient internalization. We also find that lower membrane bending rigidity may help promote the bioparticle entry. Research reported in this publication was supported by the National Institute of General Medical Sciences of the National Institutes of Health under Award Number R01GM122081.

Regulation of energy partitioning and alternative electron transport pathways during cold acclimation of lodgepole pine is oxygen dependent.

Science.gov (United States)

Savitch, Leonid V; Ivanov, Alexander G; Krol, Marianna; Sprott, David P; Oquist, Gunnar; Huner, Norman P A

2010-09-01

Second year needles of Lodgepole pine (Pinus contorta L.) were exposed for 6 weeks to either simulated control summer ['summer'; 25 °C/250 photon flux denisty (PFD)], autumn ('autumn'; 15°C/250 PFD) or winter conditions ('winter'; 5 °C/250 PFD). We report that the proportion of linear electron transport utilized in carbon assimilation (ETR(CO2)) was 40% lower in both 'autumn' and 'winter' pine when compared with the 'summer' pine. In contrast, the proportion of excess photosynthetic linear electron transport (ETR(excess)) not used for carbon assimilation within the total ETR(Jf) increased by 30% in both 'autumn' and 'winter' pine. In 'autumn' pine acclimated to 15°C, the increased amounts of 'excess' electrons were directed equally to 21  kPa O2-dependent and 2  kPa O2-dependent alternative electron transport pathways and the fractions of excitation light energy utilized by PSII photochemistry (Φ(PSII)), thermally dissipated through Φ(NPQ) and dissipated by additional quenching mechanism(s) (Φ(f,D)) were similar to those in 'summer' pine. In contrast, in 'winter' needles acclimated to 5 °C, 60% of photosynthetically generated 'excess' electrons were utilized through the 2  kPa O2-dependent electron sink and only 15% by the photorespiratory (21  kPa O2) electron pathway. Needles exposed to 'winter' conditions led to a 3-fold lower Φ(PSII), only a marginal increase in Φ(NPQ) and a 2-fold higher Φ(f,D), which was O2 dependent compared with the 'summer' and 'autumn' pine. Our results demonstrate that the employment of a variety of alternative pathways for utilization of photosynthetically generated electrons by Lodgepole pine depends on the acclimation temperature. Furthermore, dissipation of excess light energy through constitutive non-photochemical quenching mechanisms is O2 dependent.

Volvo ja Ikea endine tegevjuht Göran Carstedt : Tänapäevane (personali)juhtimine peab sisaldama eeskätt looduslähedast mõtteviisi / Göran Carstedt ; interv. Tiina Saar

Index Scriptorium Estoniae

Carstedt, Göran

2008-01-01

Juhtimiskonsultant ning Organisatsioonilise Õppimise Ühingu eestvedaja ja arendaja Göran Carsedt vastab küsimustele, mis puudutavad ettevõtte tegevust personali tööle pühendumise parendamiseks, ettevõtte jätkusuutlikku juhtimist ja tootlikkust, majanduslanguse mõju ettevõtete personalipoliitikale, talendijuhtimist, väikeste ettevõttete ellujäämist majanduslanguse ajal, IKEA kui hea tööandja mainet ning jätkusuutlikku personaliarendajat. Lisa: Jätkusuutlik juhtimine Rootsi moodi

Comparisons of LES and RANS Computations with PIV Experiments on a Cylindrical Cavity Flow

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Wen-Tao Su

2013-01-01

Full Text Available A comparison study on the numerical computations by large eddy simulation (LES and Reynolds-averaged Navier-Stokes (RANS methods with experiment on a cylindrical cavity flow was conducted in this paper. Numerical simulations and particle image velocimetry (PIV measurement were performed for two Reynolds numbers of the flow at a constant aspect ratio of H/R = 2.4 (R is the radius of the cylindrical cavity, and H is liquid level. The three components of velocity were extracted from 100 sequential PIV measured velocity frames with averaging, in order to illustrate the axial jet flow evolution and circulation distribution in the radial direction. The results show that LES can reproduce well the fine structure inside the swirling motions in both the meridional and the horizontal planes, as well as the distributions of velocity components and the circulation, in good agreement with experimental results, while the RANS method only provided a rough trend of inside vortex structure. Based on the analysis of velocity profiles at various locations, it indicates that LES is more suitable for predicting the complex flow characteristics inside complicated three-dimensional geometries.

Exploring the Leishmania Hydrophilic Acylated Surface Protein B (HASPB) Export Pathway by Live Cell Imaging Methods.

Science.gov (United States)

MacLean, Lorna; Price, Helen; O'Toole, Peter

2016-01-01

Leishmania major is a human-infective protozoan parasite transmitted by the bite of the female phlebotomine sand fly. The L. major hydrophilic acylated surface protein B (HASPB) is only expressed in infective parasite stages suggesting a role in parasite virulence. HASPB is a "nonclassically" secreted protein that lacks a conventional signal peptide, reaching the cell surface by an alternative route to the classical ER-Golgi pathway. Instead HASPB trafficking to and exposure on the parasite plasma membrane requires dual N-terminal acylation. Here, we use live cell imaging methods to further explore this pathway allowing visualization of key events in real time at the individual cell level. These methods include live cell imaging using fluorescent reporters to determine the subcellular localization of wild type and acylation site mutation HASPB18-GFP fusion proteins, fluorescence recovery after photobleaching (FRAP) to analyze the dynamics of HASPB in live cells, and live antibody staining to detect surface exposure of HASPB by confocal microscopy.

NATO Advanced Research Workshop on Squeezed and Non-classical Light

CERN Document Server

Pike, E; Squeezed and Non-classical Light

1988-01-01

The recent generation in the laboratory of phase squeezed and intensity squeezed light beams has brought to fruition the theoretical predictions of such non-classical phenomena which have been made and developed in recent years by a number of workers in the field of quantum optics. A vigorous development is now underway of both theory and experiment and the first measurements have been coi:Jfirmed and extended already in some half dozen laboratories. Although the fields of application of these novellight sources are as yet somewhat hazy in our minds and some inspired thinking is required along these lines, the pace and excitement of the research is very clear. It is to he hoped that the new possibilities of: making measurements below the quantum shot noise lirnit which is made possible by these squeezed states of light willlead to further fundamental advances in the near future. In this NATO ARW a number of the leaders in the field met in the extremely pleasant surroundings of Cortina d'Ampezzo and th...

Non-classical neutron beams for fundamental and solid state research

International Nuclear Information System (INIS)

Rauch, H.

2008-01-01

The curious dual nature of the neutron, sometimes a particle, sometimes a wave, is wonderfully manifested in the various non-local interference and quantum contextuality effects observed in neutron interferometry. Non-classical states may become useful for novel fundamental and solid state research. Here we discuss unavoidable quantum losses as they appear in neutron phase-echo and spin rotation experiments and we show how entanglement effects in a single particle system demonstrate quantum contextuality. In all cases of interactions, parasitic beams are produced which cannot be recombined completely with the original beam. This means that a complete reconstruction of the original state would, in principle, be impossible which causes a kind of intrinsic irreversibility. Even small interaction potentials can have huge effects when they are applied in quantum Zeno-like experiments. Recently, it has been shown that an entanglement between external and internal degrees of freedom exists even in single particle systems. This contextuality phenomenon also shows that a quantum system carries much more information than usually extracted. The path towards advanced neutron quantum optics will be discussed. (author)

Entanglement swapping of noisy states: A kind of superadditivity in nonclassicality

International Nuclear Information System (INIS)

Sen, Aditi; Sen, Ujjwal; Brukner, Caslav; Buzek, Vladimir; Zukowski, Marek

2005-01-01

We address the question as to whether an entangled state that satisfies local realism will give a violation of the same after entanglement swapping in a suitable scenario. We consider such a possibility as a kind of superadditivity in nonclassicality. Importantly, it will indicate that checking for violation of local realism, in the state obtained after entanglement swapping, can be a method for detecting entanglement in the input state of the swapping procedure. We investigate various entanglement swapping schemes, which involve mixed initial states. The strength of violation of local realism by the state obtained after entanglement swapping is compared with the one for the input states. We obtain a kind of superadditivity of violation of local realism for Werner states, consequent upon entanglement swapping involving Greenberger-Horne-Zeilinger-state measurements. We also discuss whether entanglement swapping of specific states may be used in quantum repeaters with a substantially reduced need to perform the entanglement distillation step

Activity-Dependent Bidirectional Regulation of GAD Expression in a Homeostatic Fashion Is Mediated by BDNF-Dependent and Independent Pathways

Science.gov (United States)

Hanno-Iijima, Yoko; Tanaka, Masami; Iijima, Takatoshi

2015-01-01

Homeostatic synaptic plasticity, or synaptic scaling, is a mechanism that tunes neuronal transmission to compensate for prolonged, excessive changes in neuronal activity. Both excitatory and inhibitory neurons undergo homeostatic changes based on synaptic transmission strength, which could effectively contribute to a fine-tuning of circuit activity. However, gene regulation that underlies homeostatic synaptic plasticity in GABAergic (GABA, gamma aminobutyric) neurons is still poorly understood. The present study demonstrated activity-dependent dynamic scaling in which NMDA-R (N-methyl-D-aspartic acid receptor) activity regulated the expression of GABA synthetic enzymes: glutamic acid decarboxylase 65 and 67 (GAD65 and GAD67). Results revealed that activity-regulated BDNF (brain-derived neurotrophic factor) release is necessary, but not sufficient, for activity-dependent up-scaling of these GAD isoforms. Bidirectional forms of activity-dependent GAD expression require both BDNF-dependent and BDNF-independent pathways, both triggered by NMDA-R activity. Additional results indicated that these two GAD genes differ in their responsiveness to chronic changes in neuronal activity, which could be partially caused by differential dependence on BDNF. In parallel to activity-dependent bidirectional scaling in GAD expression, the present study further observed that a chronic change in neuronal activity leads to an alteration in neurotransmitter release from GABAergic neurons in a homeostatic, bidirectional fashion. Therefore, the differential expression of GAD65 and 67 during prolonged changes in neuronal activity may be implicated in some aspects of bidirectional homeostatic plasticity within mature GABAergic presynapses. PMID:26241953

Renin-angiotensin system: an old player with novel functions in skeletal muscle.

Science.gov (United States)

Cabello-Verrugio, Claudio; Morales, María Gabriela; Rivera, Juan Carlos; Cabrera, Daniel; Simon, Felipe

2015-05-01

Skeletal muscle is a tissue that shows the most plasticity in the body; it can change in response to physiological and pathological stimuli. Among the diseases that affect skeletal muscle are myopathy-associated fibrosis, insulin resistance, and muscle atrophy. A common factor in these pathologies is the participation of the renin-angiotensin system (RAS). This system can be functionally separated into the classical and nonclassical RAS axis. The main components of the classical RAS pathway are angiotensin-converting enzyme (ACE), angiotensin II (Ang-II), and Ang-II receptors (AT receptors), whereas the nonclassical axis is composed of ACE2, angiotensin 1-7 [Ang (1-7)], and the Mas receptor. Hyperactivity of the classical axis in skeletal muscle has been associated with insulin resistance, atrophy, and fibrosis. In contrast, current evidence supports the action of the nonclassical RAS as a counter-regulator axis of the classical RAS pathway in skeletal muscle. In this review, we describe the mechanisms involved in the pathological effects of the classical RAS, advances in the use of pharmacological molecules to inhibit this axis, and the beneficial effects of stimulation of the nonclassical RAS pathway on insulin resistance, atrophy, and fibrosis in skeletal muscle. © 2015 Wiley Periodicals, Inc.

Estrogens induce rapid cytoskeleton re-organization in human dermal fibroblasts via the non-classical receptor GPR30.

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Julie Carnesecchi

Full Text Available The post-menopausal decrease in estrogen circulating levels results in rapid skin deterioration pointing out to a protective effect exerted by these hormones. The identity of the skin cell type responding to estrogens is unclear as are the cellular and molecular processes they elicit. Here, we reported that lack of estrogens induces rapid re-organization of the human dermal fibroblast cytoskeleton resulting in striking cell shape change. This morphological change was accompanied by a spatial re-organization of focal adhesion and a substantial reduction of their number as evidenced by vinculin and actin co-staining. Cell morphology and cytoskeleton organization was fully restored upon 17β-estradiol (E2 addition. Treatment with specific ER antagonists and cycloheximide respectively showed that the E2 acts independently of the classical Estrogen Receptors and that cell shape change is mediated by non-genomic mechanisms. E2 treatment resulted in a rapid and transient activation of ERK1/2 but not Src or PI3K. We show that human fibroblasts express the non-classical E2 receptor GPR30 and that its agonist G-1 phenocopies the effect of E2. Inhibiting GPR30 through treatment with the G-15 antagonist or specific shRNA impaired E2 effects. Altogether, our data reveal a novel mechanism by which estrogens act on skin fibroblast by regulating cell shape through the non-classical G protein-coupled receptor GPR30 and ERK1/2 activation.

Estrogens induce rapid cytoskeleton re-organization in human dermal fibroblasts via the non-classical receptor GPR30.

Science.gov (United States)

Carnesecchi, Julie; Malbouyres, Marilyne; de Mets, Richard; Balland, Martial; Beauchef, Gallic; Vié, Katell; Chamot, Christophe; Lionnet, Claire; Ruggiero, Florence; Vanacker, Jean-Marc

2015-01-01

The post-menopausal decrease in estrogen circulating levels results in rapid skin deterioration pointing out to a protective effect exerted by these hormones. The identity of the skin cell type responding to estrogens is unclear as are the cellular and molecular processes they elicit. Here, we reported that lack of estrogens induces rapid re-organization of the human dermal fibroblast cytoskeleton resulting in striking cell shape change. This morphological change was accompanied by a spatial re-organization of focal adhesion and a substantial reduction of their number as evidenced by vinculin and actin co-staining. Cell morphology and cytoskeleton organization was fully restored upon 17β-estradiol (E2) addition. Treatment with specific ER antagonists and cycloheximide respectively showed that the E2 acts independently of the classical Estrogen Receptors and that cell shape change is mediated by non-genomic mechanisms. E2 treatment resulted in a rapid and transient activation of ERK1/2 but not Src or PI3K. We show that human fibroblasts express the non-classical E2 receptor GPR30 and that its agonist G-1 phenocopies the effect of E2. Inhibiting GPR30 through treatment with the G-15 antagonist or specific shRNA impaired E2 effects. Altogether, our data reveal a novel mechanism by which estrogens act on skin fibroblast by regulating cell shape through the non-classical G protein-coupled receptor GPR30 and ERK1/2 activation.

Maraviroc attenuates trauma-hemorrhage-induced hepatic injury through PPAR gamma-dependent pathway in rats.

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Fu-Chao Liu

Full Text Available Maraviroc is a CC-chemokine receptor 5 (CCR5 antagonist with potent antiviral and cancer preventive effects. Recent evidence suggests that the co-existence of CCR5 in various cell types is involved in inflammation. However, the effects that CCR5 antagonists produce in trauma-hemorrhage remain unknown. The peroxisome proliferator-activated receptor gamma (PPAR(γ pathway exerts anti-inflammatory effects in injury. In this study, we hypothesized that maraviroc administration in male rats, after trauma-hemorrhage, decreases cytokine production and protects against hepatic injury through a PPAR(γ-dependent pathway. Male Sprague-Dawley rats underwent trauma-hemorrhage (mean blood pressure maintained at approximately 35-40 mmHg for 90 minutes, followed by fluid resuscitation. During resuscitation, a single dose of maraviroc (3 mg/kg, intravenously with and without a PPAR(γ antagonist GW9662 (1 mg/kg, intravenously, GW9662 or vehicle was administered. Plasma alanine aminotransferase (ALT with aspartate aminotransferase (AST concentrations and various hepatic parameters were measured (n=8 rats/group at 24 hours after resuscitation. The results showed that trauma-hemorrhage increased hepatic myeloperoxidase activity, intercellular adhesion molecule-1 and interleukin-6 levels, and plasma ALT and AST concentrations. These parameters were significantly improved in the maraviroc-treated rats subjected to trauma-hemorrhage. Maraviroc treatment also increased hepatic PPAR(γ expression compared with vehicle-treated trauma-hemorrhaged rats. Co-administration of GW9662 with maraviroc abolished the maraviroc-induced beneficial effects on the above parameters and hepatic injury. These results suggest that the protective effect of maraviroc administration on alleviation of hepatic injury after trauma-hemorrhage, which is, at least in part, through PPAR(γ-dependent pathway.

Statistical Multiplexing of Computations in C-RAN with Tradeoffs in Latency and Energy

OpenAIRE

Kalør, Anders E.; Agurto, Mauricio I.; Pratas, Nuno K.; Nielsen, Jimmy J.; Popovski, Petar

2017-01-01

In the Cloud Radio Access Network (C-RAN) architecture, the baseband signals from multiple remote radio heads are processed in a centralized baseband unit (BBU) pool. This architecture allows network operators to adapt the BBU’scomputational resources to the aggregate access load experienced at the BBU, which can change in every air-interface access frame. The degree of savings that can be achieved by adapting the resources is a tradeoff between savings, adaptation frequency, and increased qu...

Multi-crack imaging using nonclassical nonlinear acoustic method

International Nuclear Information System (INIS)

Zhang Lue; Zhang Ying; Liu Xiao-Zhou; Gong Xiu-Fen

2014-01-01

Solid materials with cracks exhibit the nonclassical nonlinear acoustical behavior. The micro-defects in solid materials can be detected by nonlinear elastic wave spectroscopy (NEWS) method with a time-reversal (TR) mirror. While defects lie in viscoelastic solid material with different distances from one another, the nonlinear and hysteretic stress—strain relation is established with Preisach—Mayergoyz (PM) model in crack zone. Pulse inversion (PI) and TR methods are used in numerical simulation and defect locations can be determined from images obtained by the maximum value. Since false-positive defects might appear and degrade the imaging when the defects are located quite closely, the maximum value imaging with a time window is introduced to analyze how defects affect each other and how the fake one occurs. Furthermore, NEWS-TR-NEWS method is put forward to improve NEWS-TR scheme, with another forward propagation (NEWS) added to the existing phases (NEWS and TR). In the added phase, scanner locations are determined by locations of all defects imaged in previous phases, so that whether an imaged defect is real can be deduced. NEWS-TR-NEWS method is proved to be effective to distinguish real defects from the false-positive ones. Moreover, it is also helpful to detect the crack that is weaker than others during imaging procedure. (electromagnetism, optics, acoustics, heat transfer, classical mechanics, and fluid dynamics)

Uncoupling phototoxicity-elicited neural dysmorphology and death by insidious function and selective impairment of Ran-binding protein 2 (Ranbp2).

Science.gov (United States)

Cho, Kyoung-in; Haney, Victoria; Yoon, Dosuk; Hao, Yin; Ferreira, Paulo A

2015-12-21

Morphological disintegration of neurons is coupled invariably to neural death. In particular, disruption of outer segments of photoreceptor neurons triggers photoreceptor death regardless of the pathological stressors. We show that Ranbp2(-/-)::Tg-Ranbp2(CLDm-HA) mice with mutations in SUMO-binding motif (SBM) of cyclophilin-like domain (CLD) of Ran-binding protein 2 (Ranbp2) expressed in a null Ranbp2 background lack untoward effects in photoreceptors in the absence of light-stress. However, compared to wild type photoreceptors, light-stress elicits profound disintegration of outer segments of Ranbp2(-/-)::Tg-Ranbp2(CLDm-HA) with paradoxical age-dependent resistance of photoreceptors to death and genotype-independent activation of caspases. Ranbp2(-/-)::Tg-Ranbp2(CLDm-HA) exhibit photoreceptor death-independent changes in ubiquitin-proteasome system (UPS), but death-dependent increase of ubiquitin carrier protein 9(ubc9) levels. Hence, insidious functional impairment of SBM of Ranbp2's CLD promotes neuroprotection and uncoupling of photoreceptor degeneration and death against phototoxicity. Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Thermal Stress Analysis of a Continuous and Pulsed End-Pumped Nd:YAG Rod Crystal Using Non-Classic Conduction Heat Transfer Theory

Science.gov (United States)

Mojahedi, Mahdi; Shekoohinejad, Hamidreza

2018-02-01

In this paper, temperature distribution in the continuous and pulsed end-pumped Nd:YAG rod crystal is determined using nonclassical and classical heat conduction theories. In order to find the temperature distribution in crystal, heat transfer differential equations of crystal with consideration of boundary conditions are derived based on non-Fourier's model and temperature distribution of the crystal is achieved by an analytical method. Then, by transferring non-Fourier differential equations to matrix equations, using finite element method, temperature and stress of every point of crystal are calculated in the time domain. According to the results, a comparison between classical and nonclassical theories is represented to investigate rupture power values. In continuous end pumping with equal input powers, non-Fourier theory predicts greater temperature and stress compared to Fourier theory. It also shows that with an increase in relaxation time, crystal rupture power decreases. Despite of these results, in single rectangular pulsed end-pumping condition, with an equal input power, Fourier theory indicates higher temperature and stress rather than non-Fourier theory. It is also observed that, when the relaxation time increases, maximum amounts of temperature and stress decrease.

Microenvironment Dependent Photobiomodulation on Function-Specific Signal Transduction Pathways

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Timon Cheng-Yi Liu

2014-01-01

Full Text Available Cellular photobiomodulation on a cellular function has been shown to be homeostatic. Its function-specific pathway mechanism would be further discussed in this paper. The signal transduction pathways maintaining a normal function in its function-specific homeostasis (FSH, resisting the activation of many other irrelative signal transduction pathways, are so sparse that it can be supposed that there may be normal function-specific signal transduction pathways (NSPs. A low level laser irradiation or monochromatic light may promote the activation of partially activated NSP and/or its redundant NSP so that it may induce the second-order phase transition of a function from its dysfunctional one far from its FSH to its normal one in a function-specific microenvironment and may also induce the first-order functional phase transition of the normal function from low level to high level.

Epigallocatechin-3-Gallate (EGCG Promotes Autophagy-Dependent Survival via Influencing the Balance of mTOR-AMPK Pathways upon Endoplasmic Reticulum Stress

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Marianna Holczer

2018-01-01

Full Text Available The maintenance of cellular homeostasis is largely dependent on the ability of cells to give an adequate response to various internal and external stimuli. We have recently proposed that the life-and-death decision in endoplasmic reticulum (ER stress response is defined by a crosstalk between autophagy, apoptosis, and mTOR-AMPK pathways, where the transient switch from autophagy-dependent survival to apoptotic cell death is controlled by GADD34. The aim of the present study was to investigate the role of epigallocatechin-3-gallate (EGCG, the major polyphenol of green tea, in promoting autophagy-dependent survival and to verify the key role in connecting GADD34 with mTOR-AMPK pathways upon prolonged ER stress. Our findings, obtained by using HEK293T cells, revealed that EGCG treatment is able to extend cell viability by inducing autophagy. We confirmed that EGCG-induced autophagy is mTOR-dependent and PKA-independent; furthermore, it also required ULK1. We show that pretreatment of cells with EGCG diminishes the negative effect of GADD34 inhibition (by guanabenz or siGADD34 treatment on autophagy. EGCG was able to delay apoptotic cell death by upregulating autophagy-dependent survival even in the absence of GADD34. Our data suggest a novel role for EGCG in promoting cell survival via shifting the balance of mTOR-AMPK pathways in ER stress.

Path dependence and creation

DEFF Research Database (Denmark)

Garud, Raghu; Karnøe, Peter

This edited volume stems from a conference held in Copenhagen that the authors ran in August of 1997. The authors, aware of the recent work in evolutionary theory and the science of chaos and complexity, challenge the sometimes deterministic flavour of this work. They are interested in uncovering...... the place of agency in these theories that take history so seriously. In the end, they are as interested in path creation and destruction as they are in path dependence. This book is compiled of both theoretical and empirical writing. It shows relatively well-known industries such as the automobile...

Application of the order-of-magnitude analysis to a fourth-order RANS closure for simulating a 2D boundary layer

Science.gov (United States)

Poroseva, Svetlana V.

2013-11-01

Simulations of turbulent boundary-layer flows are usually conducted using a set of the simplified Reynolds-Averaged Navier-Stokes (RANS) equations obtained by order-of-magnitude analysis (OMA) of the original RANS equations. The resultant equations for the mean-velocity components are closed using the Boussinesq approximation for the Reynolds stresses. In this study OMA is applied to the fourth-order RANS (FORANS) set of equations. The FORANS equations are chosen as they can be closed on the level of the 5th-order correlations without using unknown model coefficients, i.e. no turbulent diffusion modeling is required. New models for the 2nd-, 3rd- and 4th-order velocity-pressure gradient correlations are derived for the current FORANS equations. This set of FORANS equations and models are analyzed for the case of two-dimensional mean flow. The equations include familiar transport terms for the mean-velocity components along with algebraic expressions for velocity correlations of different orders specific to the FORANS approach. Flat plate DNS data (Spalart, 1988) are used to verify these expressions and the areas of the OMA applicability within the boundary layer. The material is based upon work supported by NASA under award NNX12AJ61A.

Hydrogen peroxide induces activation of insulin signaling pathway via AMP-dependent kinase in podocytes

International Nuclear Information System (INIS)

Piwkowska, Agnieszka; Rogacka, Dorota; Angielski, Stefan; Jankowski, Maciej

2012-01-01

Highlights: ► H 2 O 2 activates the insulin signaling pathway and glucose uptake in podocytes. ► H 2 O 2 induces time-dependent changes in AMPK phosphorylation. ► H 2 O 2 enhances insulin signaling pathways via AMPK activation. ► H 2 O 2 stimulation of glucose uptake is AMPK-dependent. -- Abstract: Podocytes are cells that form the glomerular filtration barrier in the kidney. Insulin signaling in podocytes is critical for normal kidney function. Insulin signaling is regulated by oxidative stress and intracellular energy levels. We cultured rat podocytes to investigate the effects of hydrogen peroxide (H 2 O 2 ) on the phosphorylation of proximal and distal elements of insulin signaling. We also investigated H 2 O 2 -induced intracellular changes in the distribution of protein kinase B (Akt). Western blots showed that H 2 O 2 (100 μM) induced rapid, transient phosphorylation of the insulin receptor (IR), the IR substrate-1 (IRS1), and Akt with peak activities at 5 min (Δ 183%, P 2 O 2 >. Furthermore, H 2 O 2 inhibited phosphorylation of the phosphatase and tensin homologue (PTEN; peak activity at 10 min; Δ −32%, P 2 O 2 on IR phosphorylation by about 40% (from 2.07 ± 0.28 to 1.28 ± 0.12, P 2 O 2 increased glucose uptake in podocytes (from 0.88 ± 0.04 to 1.29 ± 0.12 nmol/min/mg protein, P 2 O 2 activated the insulin signaling pathway and glucose uptake via AMPK in cultured rat podocytes. This signaling may play a potential role in the prevention of insulin resistance under conditions associated with oxidative stress.

Caspase-1-dependent and -independent cell death pathways in Burkholderia pseudomallei infection of macrophages.

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Antje Bast

2014-03-01

Full Text Available The cytosolic pathogen Burkholderia pseudomallei and causative agent of melioidosis has been shown to regulate IL-1β and IL-18 production through NOD-like receptor NLRP3 and pyroptosis via NLRC4. Downstream signalling pathways of those receptors and other cell death mechanisms induced during B. pseudomallei infection have not been addressed so far in detail. Furthermore, the role of B. pseudomallei factors in inflammasome activation is still ill defined. In the present study we show that caspase-1 processing and pyroptosis is exclusively dependent on NLRC4, but not on NLRP3 in the early phase of macrophage infection, whereas at later time points caspase-1 activation and cell death is NLRC4- independent. In the early phase we identified an activation pathway involving caspases-9, -7 and PARP downstream of NLRC4 and caspase-1. Analyses of caspase-1/11-deficient infected macrophages revealed a strong induction of apoptosis, which is dependent on activation of apoptotic initiator and effector caspases. The early activation pathway of caspase-1 in macrophages was markedly reduced or completely abolished after infection with a B. pseudomallei flagellin FliC or a T3SS3 BsaU mutant. Studies using cells transfected with the wild-type and mutated T3SS3 effector protein BopE indicated also a role of this protein in caspase-1 processing. A T3SS3 inner rod protein BsaK mutant failed to activate caspase-1, revealed higher intracellular counts, reduced cell death and IL-1β secretion during early but not during late macrophage infection compared to the wild-type. Intranasal infection of BALB/c mice with the BsaK mutant displayed a strongly decreased mortality, lower bacterial loads in organs, and reduced levels of IL-1β, myeloperoxidase and neutrophils in bronchoalveolar lavage fluid. In conclusion, our results indicate a major role for a functional T3SS3 in early NLRC4-mediated caspase-1 activation and pyroptosis and a contribution of late caspase-1

Reduced RAN expression and disrupted transport between cytoplasm and nucleus; a key event in Alzheimer's disease pathophysiology.

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Diego Mastroeni

Full Text Available Transcription of DNA is essential for cell maintenance and survival; inappropriate localization of proteins that are involved in transcription would be catastrophic. In Alzheimer's disease brains, and in vitro studies, we have found qualitative and quantitative deficits in transport into the nucleus of DNA methyltransferase 1 (DNMT1 and RNA polymerase II (RNA pol II, accompanied by their abnormal sequestration in the cytoplasm. RAN (RAs-related Nuclear protein knockdown, by siRNA and oligomeric Aβ42 treatment in neurons, replicate human data which indicate that transport disruption in AD may be mechanistically linked to reduced expression of RAN, a pivotal molecule in nucleocytoplasmic transport. In vitro studies also indicate a significant role for oligomeric Aβ42 in the observed phenomena. We propose a model in which reduced transcription regulators in the nucleus and their increased presence in the cytoplasm may lead to many of the cellular manifestations of Alzheimer's disease.

Activation of the Cph1-dependent MAP kinase signaling pathway induces white-opaque switching in Candida albicans.

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Bernardo Ramírez-Zavala

Full Text Available Depending on the environmental conditions, the pathogenic yeast Candida albicans can undergo different developmental programs, which are controlled by dedicated transcription factors and upstream signaling pathways. C. albicans strains that are homozygous at the mating type locus can switch from the normal yeast form (white to an elongated cell type (opaque, which is the mating-competent form of this fungus. Both white and opaque cells use the Ste11-Hst7-Cek1/Cek2 MAP kinase signaling pathway to react to the presence of mating pheromone. However, while opaque cells employ the transcription factor Cph1 to induce the mating response, white cells recruit a different downstream transcription factor, Tec1, to promote the formation of a biofilm that facilitates mating of opaque cells in the population. The switch from the white to the opaque cell form is itself induced by environmental signals that result in the upregulation of the transcription factor Wor1, the master regulator of white-opaque switching. To get insight into the upstream signaling pathways controlling the switch, we expressed all C. albicans protein kinases from a tetracycline-inducible promoter in a switching-competent strain. Screening of this library of strains showed that a hyperactive form of Ste11 lacking its N-terminal domain (Ste11(ΔN467 efficiently stimulated white cells to switch to the opaque phase, a behavior that did not occur in response to pheromone. Ste11(ΔN467-induced switching specifically required the downstream MAP kinase Cek1 and its target transcription factor Cph1, but not Cek2 and Tec1, and forced expression of Cph1 also promoted white-opaque switching in a Wor1-dependent manner. Therefore, depending on the activation mechanism, components of the pheromone-responsive MAP kinase pathway can be reconnected to stimulate an alternative developmental program, switching of white cells to the mating-competent opaque phase.

Transcriptome analysis of tobacco BY-2 cells elicited by cryptogein reveals new potential actors of calcium-dependent and calcium-independent plant defense pathways.

Science.gov (United States)

Amelot, Nicolas; Dorlhac de Borne, François; San Clemente, Hélène; Mazars, Christian; Grima-Pettenati, Jacqueline; Brière, Christian

2012-02-01

Cryptogein is a proteinaceous elicitor secreted by the oomycete Phytophthora cryptogea, which induces a hypersensitive response in tobacco plants. We have previously reported that in tobacco BY-2 cells treated with cryptogein, most of the genes of the phenylpropanoid pathway were upregulated and cell wall-bound phenolics accumulated. Both events were Ca(2+) dependent. In this study, we designed a microarray covering a large proportion of the tobacco genome and monitored gene expression in cryptogein-elicited BY-2 cells to get a more complete view of the transcriptome changes and to assess their Ca(2+) dependence. The predominant functional gene categories affected by cryptogein included stress- and disease-related proteins, phenylpropanoid pathway, signaling components, transcription factors and cell wall reinforcement. Among the 3819 unigenes whose expression changed more than fourfold, 90% were Ca(2+) dependent, as determined by their sensitivity to lanthanum chloride. The most Ca(2+)-dependent transcripts upregulated by cryptogein were involved in defense responses or the oxylipin pathway. This genome-wide study strongly supports the importance of Ca(2+)-dependent transcriptional regulation of regulatory and defense-related genes contributing to cryptogein responses in tobacco. Copyright © 2011 Elsevier Ltd. All rights reserved.

Chem/bio sensing with non-classical light and integrated photonics.

Science.gov (United States)

Haas, J; Schwartz, M; Rengstl, U; Jetter, M; Michler, P; Mizaikoff, B

2018-01-29

Modern quantum technology currently experiences extensive advances in applicability in communications, cryptography, computing, metrology and lithography. Harnessing this technology platform for chem/bio sensing scenarios is an appealing opportunity enabling ultra-sensitive detection schemes. This is further facilliated by the progress in fabrication, miniaturization and integration of visible and infrared quantum photonics. Especially, the combination of efficient single-photon sources together with waveguiding/sensing structures, serving as active optical transducer, as well as advanced detector materials is promising integrated quantum photonic chem/bio sensors. Besides the intrinsic molecular selectivity and non-destructive character of visible and infrared light based sensing schemes, chem/bio sensors taking advantage of non-classical light sources promise sensitivities beyond the standard quantum limit. In the present review, recent achievements towards on-chip chem/bio quantum photonic sensing platforms based on N00N states are discussed along with appropriate recognition chemistries, facilitating the detection of relevant (bio)analytes at ultra-trace concentration levels. After evaluating recent developments in this field, a perspective for a potentially promising sensor testbed is discussed for reaching integrated quantum sensing with two fiber-coupled GaAs chips together with semiconductor quantum dots serving as single-photon sources.

Exosome uptake depends on ERK1/2-heat shock protein 27 signaling and lipid Raft-mediated endocytosis negatively regulated by caveolin-1.

Science.gov (United States)

Svensson, Katrin J; Christianson, Helena C; Wittrup, Anders; Bourseau-Guilmain, Erika; Lindqvist, Eva; Svensson, Lena M; Mörgelin, Matthias; Belting, Mattias

2013-06-14

The role of exosomes in cancer can be inferred from the observation that they transfer tumor cell derived genetic material and signaling proteins, resulting in e.g. increased tumor angiogenesis and metastasis. However, the membrane transport mechanisms and the signaling events involved in the uptake of these virus-like particles remain ill-defined. We now report that internalization of exosomes derived from glioblastoma (GBM) cells involves nonclassical, lipid raft-dependent endocytosis. Importantly, we show that the lipid raft-associated protein caveolin-1 (CAV1), in analogy with its previously described role in virus uptake, negatively regulates the uptake of exosomes. We find that exosomes induce the phosphorylation of several downstream targets known to associate with lipid rafts as signaling and sorting platforms, such as extracellular signal-regulated kinase-1/2 (ERK1/2) and heat shock protein 27 (HSP27). Interestingly, exosome uptake appears dependent on unperturbed ERK1/2-HSP27 signaling, and ERK1/2 phosphorylation is under negative influence by CAV1 during internalization of exosomes. These findings significantly advance our general understanding of exosome-mediated uptake and offer potential strategies for how this pathway may be targeted through modulation of CAV1 expression and ERK1/2 signaling.

Optimizing small cell deployment by the use of C-RANs

DEFF Research Database (Denmark)

Checko, Aleksandra; Holm, Henrik Laumand; Christiansen, Henrik Lehrmann

2014-01-01

A Cloud Radio Access Network (C-RAN) is a novel mobile network architecture that has the potential to support extremely dense mobile network deployments enhancing the network capacity while offering cost savings on baseband resources. In this work we analyze cell traffic profiles and evaluate...... the conditions that impact the statistical multiplexing gain in the Baseband Unit (BBU) Pool. We conclude on the set of parameters that maximize the statistical multiplexing gain, leading to the highest potential cost savings. We then propose a packet based architecture that can adapt to changing traffic...... conditions. Furthermore, based on theoretical calculations and Network simulations we present considerations on deployment scenarios to optimize green field deployments in terms of Total Cost of Ownership (TCO). This involves optimizing the mix of cells with different traffic profiles and the BBU Pool...

Flavivirus internalization is regulated by a size-dependent endocytic pathway.

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Hackett, Brent A; Cherry, Sara

2018-04-17

Flaviviruses enter host cells through the process of clathrin-mediated endocytosis, and the spectrum of host factors required for this process are incompletely understood. Here we found that lymphocyte antigen 6 locus E (LY6E) promotes the internalization of multiple flaviviruses, including West Nile virus, Zika virus, and dengue virus. Perhaps surprisingly, LY6E is dispensable for the internalization of the endogenous cargo transferrin, which is also dependent on clathrin-mediated endocytosis for uptake. Since viruses are substantially larger than transferrin, we reasoned that LY6E may be required for uptake of larger cargoes and tested this using transferrin-coated beads of similar size as flaviviruses. LY6E was indeed required for the internalization of transferrin-coated beads, suggesting that LY6E is selectively required for large cargo. Cell biological studies found that LY6E forms tubules upon viral infection and bead internalization, and we found that tubule formation was dependent on RNASEK, which is also required for flavivirus internalization, but not transferrin uptake. Indeed, we found that RNASEK is also required for the internalization of transferrin-coated beads, suggesting it functions upstream of LY6E. These LY6E tubules resembled microtubules, and we found that microtubule assembly was required for their formation and flavivirus uptake. Since microtubule end-binding proteins link microtubules to downstream activities, we screened the three end-binding proteins and found that EB3 promotes virus uptake and LY6E tubularization. Taken together, these results highlight a specialized pathway required for the uptake of large clathrin-dependent endocytosis cargoes, including flaviviruses. Copyright © 2018 the Author(s). Published by PNAS.

Assessment of RANS CFD modelling for pressurised thermal shock analysis

International Nuclear Information System (INIS)

Sander M Willemsen; Ed MJ Komen; Sander Willemsen

2005-01-01

Full text of publication follows: The most severe Pressurised Thermal Shock (PTS) scenario is a cold water Emergency Core Coolant (ECC) injection into the cold leg during a LOCA. The injected ECC water mixes with the hot fluid present in the cold leg and flows towards the downcomer where further mixing takes place. When the cold mixture comes into contact with the Reactor Pressure Vessel (RPV) wall, it may lead to large temperature gradients and consequently to high stresses in the RPV wall. Knowledge of these thermal loads is important for RPV remnant life assessments. The existing thermal-hydraulic system codes currently applied for this purpose are based on one-dimensional approximations and can, therefore, not predict the complex three-dimensional flows occurring during ECC injection. Computational Fluid Dynamics (CFD) can be applied to predict these phenomena, with the ultimate benefit of improved remnant RPV life assessment. The present paper presents an assessment of various Reynolds Averaged Navier Stokes (RANS) CFD approaches for modeling the complex mixing phenomena occurring during ECC injection. This assessment has been performed by comparing the numerical results obtained using advanced turbulence models available in the CFX 5.6 CFD code in combination with a hybrid meshing strategy with experimental results of the Upper Plenum Test Facility (UPTF). The UPTF was a full-scale 'simulation' of the primary system of the four loop 1300 MWe Siemens/KWU Pressurised Water Reactor at Grafenrheinfeld. The test vessel upper plenum internals, downcomer and primary coolant piping were replicas of the reference plant, while other components, such as core, coolant pump and steam generators were replaced by simulators. From the extensive test programme, a single-phase fluid-fluid mixing experiment in the cold leg and downcomer was selected. Prediction of the mixing and stratification is assessed by comparison with the measured temperature profiles at several locations

Thermodynamics and Kinetics of Prenucleation Clusters, Classical and Non-Classical Nucleation.

Science.gov (United States)

Zahn, Dirk

2015-07-20

Recent observations of prenucleation species and multi-stage crystal nucleation processes challenge the long-established view on the thermodynamics of crystal formation. Here, we review and generalize extensions to classical nucleation theory. Going beyond the conventional implementation as has been used for more than a century now, nucleation inhibitors, precursor clusters and non-classical nucleation processes are rationalized as well by analogous concepts based on competing interface and bulk energy terms. This is illustrated by recent examples of species formed prior to/instead of crystal nucleation and multi-step nucleation processes. Much of the discussed insights were obtained from molecular simulation using advanced sampling techniques, briefly summarized herein for both nucleation-controlled and diffusion-controlled aggregate formation. © 2015 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the Creative Commons Attribution Non-Commercial NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Extracellular visfatin activates gluconeogenesis in HepG2 cells through the classical PKA/CREB-dependent pathway.

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Choi, Y J; Choi, S-E; Ha, E S; Kang, Y; Han, S J; Kim, D J; Lee, K W; Kim, H J

2014-04-01

Adipokines reportedly affect hepatic gluconeogenesis, and the adipokine visfatin is known to be related to insulin resistance and type 2 diabetes. However, whether visfatin contributes to hepatic gluconeogenesis remains unclear. Visfatin, also known as nicotinamide phosphoribosyltransferase (NAMPT), modulates sirtuin1 (SIRT1) through the regulation of nicotinamide adenine dinucleotide (NAD). Therefore, we investigated the effect of extracellular visfatin on glucose production in HepG2 cells, and evaluated whether extracellular visfatin affects hepatic gluconeogenesis via an NAD+-SIRT1-dependent pathway. Treatment with visfatin significantly increased glucose production and the mRNA expression and protein levels of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) in HepG2 cells in a time- and concentration-dependent manner. Knockdown of SIRT1 had no remarkable effect on the induction of gluconeogenesis by visfatin. Subsequently, we evaluated if extracellular visfatin stimulates the production of gluconeogenic enzymes through the classical protein kinase A (PKA)/cyclic AMP-responsive element (CRE)-binding protein (CREB)-dependent process. The phosphorylation of CREB and PKA increased significantly in HepG2 cells treated with visfatin. Additionally, knockdown of CREB and PKA inhibited visfatin-induced gluconeogenesis in HepG2 cells. In summary, extracellular visfatin modulates glucose production in HepG2 cells through the PKA/CREB pathway, rather than via SIRT1 signaling. © Georg Thieme Verlag KG Stuttgart · New York.

Recombinant VSV G proteins reveal a novel raft-dependent endocytic pathway in resorbing osteoclasts

International Nuclear Information System (INIS)

Mulari, Mika T.K.; Nars, Martin; Laitala-Leinonen, Tiina; Kaisto, Tuula; Metsikkoe, Kalervo; Sun Yi; Vaeaenaenen, H. Kalervo

2008-01-01

Transcytotic membrane flow delivers degraded bone fragments from the ruffled border to the functional secretory domain, FSD, in bone resorbing osteoclasts. Here we show that there is also a FSD-to-ruffled border trafficking pathway that compensates for the membrane loss during the matrix uptake process and that rafts are essential for this ruffled border-targeted endosomal pathway. Replacing the cytoplasmic tail of the vesicular stomatitis virus G protein with that of CD4 resulted in partial insolubility in Triton X-100 and retargeting from the peripheral non-bone facing plasma membrane to the FSD. Recombinant G proteins were subsequently endosytosed and delivered from the FSD to the peripheral fusion zone of the ruffled border, which were both rich in lipid rafts as suggested by viral protein transport analysis and visualizing the rafts with fluorescent recombinant cholera toxin. Cholesterol depletion by methyl-β-cyclodextrin impaired the ruffled border-targeted vesicle trafficking pathway and inhibited bone resorption dose-dependently as quantified by measuring the CTX and TRACP 5b secreted to the culture medium and by measuring the resorbed area visualized with a bi-phasic labeling method using sulpho-NHS-biotin and WGA-lectin. Thus, rafts are vital for membrane recycling from the FSD to the late endosomal/lysosomal ruffled border and bone resorption

Scaling the Drosophila Wing: TOR-Dependent Target Gene Access by the Hippo Pathway Transducer Yorkie.

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Parker, Joseph; Struhl, Gary

2015-10-01

Organ growth is controlled by patterning signals that operate locally (e.g., Wingless/Ints [Wnts], Bone Morphogenetic Proteins [BMPs], and Hedgehogs [Hhs]) and scaled by nutrient-dependent signals that act systemically (e.g., Insulin-like peptides [ILPs] transduced by the Target of Rapamycin [TOR] pathway). How cells integrate these distinct inputs to generate organs of the appropriate size and shape is largely unknown. The transcriptional coactivator Yorkie (Yki, a YES-Associated Protein, or YAP) acts downstream of patterning morphogens and other tissue-intrinsic signals to promote organ growth. Yki activity is regulated primarily by the Warts/Hippo (Wts/Hpo) tumour suppressor pathway, which impedes nuclear access of Yki by a cytoplasmic tethering mechanism. Here, we show that the TOR pathway regulates Yki by a separate and novel mechanism in the Drosophila wing. Instead of controlling Yki nuclear access, TOR signaling governs Yki action after it reaches the nucleus by allowing it to gain access to its target genes. When TOR activity is inhibited, Yki accumulates in the nucleus but is sequestered from its normal growth-promoting target genes--a phenomenon we term "nuclear seclusion." Hence, we posit that in addition to its well-known role in stimulating cellular metabolism in response to nutrients, TOR also promotes wing growth by liberating Yki from nuclear seclusion, a parallel pathway that we propose contributes to the scaling of wing size with nutrient availability.

Aryl hydrocarbon receptor pathway activation enhances gastric cancer cell invasiveness likely through a c-Jun-dependent induction of matrix metalloproteinase-9

Directory of Open Access Journals (Sweden)

Song Xin

2009-04-01

Full Text Available Abstract Background Abberant aryl hydrocarbon receptor (AhR expression and AhR pathway activation are involved in gastric carcinogenesis. However, the relationship between AhR pathway activation and gastric cancer progression is still unclear. In present study, we used 2,3,7,8-tetrachlorodibenzo-para-dioxin (TCDD, a classic and most potent ligand of AhR, to activate AhR pathway and investigated the effect of AhR pathway activation on human gastric cancer AGS cell invasion and explored the corresponding mechanism. Results To determine whether AhR pathway can be activated in AGS cells, we examined the expression of CYP1A1, a classic target gene of AhR pathway, following TCDD exposure. RT-PCR and western blot analysis showed that both CYP1A1 mRNA and protein expression were increased in a dose-dependent manner following TCDD treatment and AhR antagonist resveratrol (RSV could reverse this TCDD-induced CYP1A1 expression. To determine whether TCDD treatment of AGS cells results in an induction of MMP-9 expression, we detected MMP-9 mRNA using RT-PCR and detected MMP-9 enzymatic activity using gelatin zymography. The results showed that both MMP-9 mRNA expression and enzymatic activity were gradually increased with the concentration increase of TCDD in media and these changes could be reversed by RSV treatment in a dose-dependent manner. To examine whether AhR activation-induced MMP-9 expression and activity in AGS cells results in increased migration and invasion, we performed wound healing migration assay and transwell migration and invasion assay. After TCDD treatment, the migration distance and the migration and invasion abilities of AGS cells were increased with a dose-dependent manner. To demonstrate AhR activation-induced MMP-9 expression is mediated by c-Jun, siRNA transfection was performed to silence c-Jun mRNA in AGS cells. The results showed that MMP-9 mRNA expression and activity in untreated control AGS cells were very weak; After TCDD

Statistical Multiplexing of Computations in C-RAN with Tradeoffs in Latency and Energy

DEFF Research Database (Denmark)

Kalør, Anders Ellersgaard; Agurto Agurto, Mauricio Ignacio; Pratas, Nuno

2017-01-01

frame duration, then this may result in additional access latency and limit the energy savings. In this paper we investigate the tradeoff by considering two extreme time-scales for the resource multiplexing: (i) long-term, where the computational resources are adapted over periods much larger than...... the access frame durations; (ii) short-term, where the adaption is below the access frame duration.We develop a general C-RAN queuing model that models the access latency and show, for Poisson arrivals, that long-term multiplexing achieves savings comparable to short-term multiplexing, while offering low...

Opposing roles of RNF8/RNF168 and deubiquitinating enzymes in ubiquitination-dependent DNA double-strand break response signaling and DNA-repair pathway choice

International Nuclear Information System (INIS)

Nakada, Shinichiro

2016-01-01

The E3 ubiquitin ligases ring finger protein (RNF) 8 and RNF168 transduce the DNA double-strand break (DSB) response (DDR) signal by ubiquitinating DSB sites. The depletion of RNF8 or RNF168 suppresses the accumulation of DNA-repair regulating factors such as 53BP1 and RAP80 at DSB sites, suggesting roles for RNF8- and RNF168-mediated ubiquitination in DSB repair. This mini-review provides a brief overview of the RNF8- and RNF168-dependent DDR-signaling and DNA-repair pathways. The choice of DNA-repair pathway when RNF8- and RNF168-mediated ubiquitination-dependent DDR signaling is negatively regulated by deubiquitinating enzymes (DUBs) is reviewed to clarify how the opposing roles of RNF8/RNF168 and DUBs regulate ubiquitination-dependent DDR signaling and the choice of DNA-repair pathway

Time-dependent nonlinear Jaynes-Cummings dynamics of a trapped ion

Science.gov (United States)

Krumm, F.; Vogel, W.

2018-04-01

In quantum interaction problems with explicitly time-dependent interaction Hamiltonians, the time ordering plays a crucial role for describing the quantum evolution of the system under consideration. In such complex scenarios, exact solutions of the dynamics are rarely available. Here we study the nonlinear vibronic dynamics of a trapped ion, driven in the resolved sideband regime with some small frequency mismatch. By describing the pump field in a quantized manner, we are able to derive exact solutions for the dynamics of the system. This eventually allows us to provide analytical solutions for various types of time-dependent quantities. In particular, we study in some detail the electronic and the motional quantum dynamics of the ion, as well as the time evolution of the nonclassicality of the motional quantum state.

Several nuclear events during apoptosis depend on caspase-3 activation but do not constitute a common pathway.

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Lisa Trisciuoglio

Full Text Available A number of nuclear events occur during apoptosis, including DNA laddering, nuclear lamina breakdown, phosphorylation of histones H2B and histone H2AX, and the tight binding to chromatin of HMGB1 and CAD, the nuclease responsible for DNA laddering. We have performed an epistasis analysis to investigate whether these events cluster together in pathways. We find that all depend directly or indirectly on caspase-3 activation. CAD activation, H2AX phosphorylation and DNA laddering cluster together into a pathway, but all other events appear to be independent of each other downstream of caspase-3, and likely evolved subject to different functional pressures.

Potential involvement of drought-induced Ran GTPase CLRan1 in root growth enhancement in a xerophyte wild watermelon.

Science.gov (United States)

Akashi, Kinya; Yoshimura, Kazuya; Kajikawa, Masataka; Hanada, Kouhei; Kosaka, Rina; Kato, Atsushi; Katoh, Akira; Nanasato, Yoshihiko; Tsujimoto, Hisashi; Yokota, Akiho

2016-10-01

Enhanced root growth is known as the survival strategy of plants under drought. Previous proteome analysis in drought-resistant wild watermelon has shown that Ran GTPase, an essential regulator of cell division and proliferation, was induced in the roots under drought. In this study, two cDNAs were isolated from wild watermelon, CLRan1 and CLRan2, which showed a high degree of structural similarity with those of other plant Ran GTPases. Quantitative RT-PCR and promoter-GUS assays suggested that CLRan1 was expressed mainly in the root apex and lateral root primordia, whereas CLRan2 was more broadly expressed in other part of the roots. Immunoblotting analysis confirmed that the abundance of CLRan proteins was elevated in the root apex region under drought stress. Transgenic Arabidopsis overexpressing CLRan1 showed enhanced primary root growth, and the growth was maintained under osmotic stress, indicating that CLRan1 functions as a positive factor for maintaining root growth under stress conditions.

Validation of Heat Transfer and Film Cooling Capabilities of the 3-D RANS Code TURBO

Science.gov (United States)

Shyam, Vikram; Ameri, Ali; Chen, Jen-Ping

2010-01-01

The capabilities of the 3-D unsteady RANS code TURBO have been extended to include heat transfer and film cooling applications. The results of simulations performed with the modified code are compared to experiment and to theory, where applicable. Wilcox s k-turbulence model has been implemented to close the RANS equations. Two simulations are conducted: (1) flow over a flat plate and (2) flow over an adiabatic flat plate cooled by one hole inclined at 35 to the free stream. For (1) agreement with theory is found to be excellent for heat transfer, represented by local Nusselt number, and quite good for momentum, as represented by the local skin friction coefficient. This report compares the local skin friction coefficients and Nusselt numbers on a flat plate obtained using Wilcox's k-model with the theory of Blasius. The study looks at laminar and turbulent flows over an adiabatic flat plate and over an isothermal flat plate for two different wall temperatures. It is shown that TURBO is able to accurately predict heat transfer on a flat plate. For (2) TURBO shows good qualitative agreement with film cooling experiments performed on a flat plate with one cooling hole. Quantitatively, film effectiveness is under predicted downstream of the hole.

Hyperglycaemia-induced impairment of endothelium-dependent vasorelaxation in rat mesenteric arteries is mediated by intracellular methylglyoxal levels in a pathway dependent on oxidative stress

DEFF Research Database (Denmark)

Brouwers, O; Niessen, P M; Haenen, G

2010-01-01

-hydro-5-methylimidazolone (MG-H1) was detected with an antibody against MG-H1 and quantified with ultra-performance liquid chromatography (tandem) mass spectrometry. Reactive oxygen species formation was measured with a 5-(and-6)-chloromethyl-2'7'-dichlorodihydrofluorescein diacetate acetyl ester probe...... for AGE ligand S100b did (p cells and adventitia by fivefold accompanied by an eightfold increase in the oxidative stress marker nitrotyrosine. Antioxidant pre-incubation prevented methylglyoxal......-induced impairment of vasoreactivity. CONCLUSIONS/INTERPRETATION: These data show that hyperglycaemia-induced impairment of endothelium-dependent vasorelaxation is mediated by increased intracellular methylglyoxal levels in a pathway dependent on oxidative stress....

Characterization of novel StAR (steroidogenic acute regulatory protein mutations causing non-classic lipoid adrenal hyperplasia.

Directory of Open Access Journals (Sweden)

Christa E Flück

Full Text Available CONTEXT: Steroidogenic acute regulatory protein (StAR is crucial for transport of cholesterol to mitochondria where biosynthesis of steroids is initiated. Loss of StAR function causes lipoid congenital adrenal hyperplasia (LCAH. OBJECTIVE: StAR gene mutations causing partial loss of function manifest atypical and may be mistaken as familial glucocorticoid deficiency. Only a few mutations have been reported. DESIGN: To report clinical, biochemical, genetic, protein structure and functional data on two novel StAR mutations, and to compare them with published literature. SETTING: Collaboration between the University Children's Hospital Bern, Switzerland, and the CIBERER, Hospital Vall d'Hebron, Autonomous University, Barcelona, Spain. PATIENTS: Two subjects of a non-consanguineous Caucasian family were studied. The 46,XX phenotypic normal female was diagnosed with adrenal insufficiency at the age of 10 months, had normal pubertal development and still has no signs of hypergonodatropic hypogonadism at 32 years of age. Her 46,XY brother was born with normal male external genitalia and was diagnosed with adrenal insufficiency at 14 months. Puberty was normal and no signs of hypergonadotropic hypogonadism are present at 29 years of age. RESULTS: StAR gene analysis revealed two novel compound heterozygote mutations T44HfsX3 and G221S. T44HfsX3 is a loss-of-function StAR mutation. G221S retains partial activity (∼30% and is therefore responsible for a milder, non-classic phenotype. G221S is located in the cholesterol binding pocket and seems to alter binding/release of cholesterol. CONCLUSIONS: StAR mutations located in the cholesterol binding pocket (V187M, R188C, R192C, G221D/S seem to cause non-classic lipoid CAH. Accuracy of genotype-phenotype prediction by in vitro testing may vary with the assays employed.

Saposin C promotes survival and prevents apoptosis via PI3K/Akt-dependent pathway in prostate cancer cells

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Lee Tae-Jin

2004-11-01

Full Text Available Abstract Background In addition to androgens, growth factors are also implicated in the development and neoplastic growth of the prostate gland. Prosaposin is a potent neurotrophic molecule. Homozygous inactivation of prosaposin in mice has led to the development of a number of abnormalities in the male reproductive system, including atrophy of the prostate gland and inactivation of mitogen-activated protein kinase (MAPK and Akt in prostate epithelial cells. We have recently reported that prosaposin is expressed at a higher level by androgen-independent (AI prostate cancer cells as compared to androgen-sensitive prostate cancer cells or normal prostate epithelial and stromal cells. In addition, we have demonstrated that a synthetic peptide (prosaptide TX14A, derived from the trophic sequence of the saposin C domain of prosaposin, stimulated cell proliferation, migration and invasion and activated the MAPK signaling pathway in prostate cancer cells. The biological significances of saposin C and prosaposin in prostate cancer are not known. Results Here, we report that saposin C, in a cell type-specific and dose-dependent manner, acts as a survival factor, activates the Akt-signaling pathway, down-modulates caspase-3, -7, and -9 expression and/or activity, and decreases the cleaved nuclear substrate of caspase-3 in prostate cancer cells under serum-starvation stress. In addition, prosaptide TX14A, saposin C, or prosaposin decreased the growth-inhibitory effect, caspase-3/7 activity, and apoptotic cell death induced by etoposide. We also discovered that saposin C activates the p42/44 MAP kinase pathway in a pertussis toxin-sensitive and phosphatidylinositol 3-kinase (PI3K /Akt-dependent manner in prostate cancer cells. Our data also show that the anti-apoptotic activity of saposin C is at least partially mediated via PI3K/Akt signaling pathway. Conclusion We postulate that as a mitogenic, survival, and anti-apoptotic factor for prostate cancer cells

Activation of cAMP-dependent signaling pathway induces mouse organic anion transporting polypeptide 2 expression.

Science.gov (United States)

Chen, Chuan; Cheng, Xingguo; Dieter, Matthew Z; Tanaka, Yuji; Klaassen, Curtis D

2007-04-01

Rodent Oatp2 is a hepatic uptake transporter for such compounds as cardiac glycosides. In the present study, we found that fasting resulted in a 2-fold induction of Oatp2 expression in liver of mice. Because the cAMP-protein kinase A (PKA) signaling pathway is activated during fasting, the role of this pathway in Oatp2 induction during fasting was examined. In Hepa-1c1c7 cells, adenylyl cyclase activator forskolin as well as two cellular membrane-permeable cAMP analogs, dibutyryl cAMP and 8-bromo-cAMP, induced Oatp2 mRNA expression in a time- and dose-dependent manner. These three chemicals induced reporter gene activity in cells transfected with a luciferase reporter gene construct containing a 7.6-kilobase (kb) 5'-flanking region of mouse Oatp2. Transient transfection of cells with 5'-deletion constructs derived from the 7.6-kb Oatp2 promoter reporter gene construct, as well as 7.6-kb constructs in which a consensus cAMP response element (CRE) half-site CGTCA (-1808/-1804 bp) was mutated or deleted, confirms that this CRE site was required for the induction of luciferase activity by forskolin. Luciferase activity driven by the Oatp2 promoter containing this CRE site was induced in cells cotransfected with a plasmid encoding the protein kinase A catalytic subunit. Cotransfection of cells with a plasmid encoding the dominant-negative CRE binding protein (CREB) completely abolished the inducibility of the reporter gene activity by forskolin. In conclusion, induction of Oatp2 expression in liver of fasted mice may be caused by activation of the cAMP-dependent signaling pathway, with the CRE site (-1808/-1804) and CREB being the cis- and trans-acting factors mediating the induction, respectively.

A Mobility Management Using Follow-Me Cloud-Cloudlet in Fog-Computing-Based RANs for Smart Cities.

Science.gov (United States)

Chen, Yuh-Shyan; Tsai, Yi-Ting

2018-02-06

Mobility management for supporting the location tracking and location-based service (LBS) is an important issue of smart city by providing the means for the smooth transportation of people and goods. The mobility is useful to contribute the innovation in both public and private transportation infrastructures for smart cities. With the assistance of edge/fog computing, this paper presents a fully new mobility management using the proposed follow-me cloud-cloudlet (FMCL) approach in fog-computing-based radio access networks (Fog-RANs) for smart cities. The proposed follow-me cloud-cloudlet approach is an integration strategy of follow-me cloud (FMC) and follow-me edge (FME) (or called cloudlet). A user equipment (UE) receives the data, transmitted from original cloud, into the original edge cloud before the handover operation. After the handover operation, an UE searches for a new cloud, called as a migrated cloud, and a new edge cloud, called as a migrated edge cloud near to UE, where the remaining data is migrated from the original cloud to the migrated cloud and all the remaining data are received in the new edge cloud. Existing FMC results do not have the property of the VM migration between cloudlets for the purpose of reducing the transmission latency, and existing FME results do not keep the property of the service migration between data centers for reducing the transmission latency. Our proposed FMCL approach can simultaneously keep the VM migration between cloudlets and service migration between data centers to significantly reduce the transmission latency. The new proposed mobility management using FMCL approach aims to reduce the total transmission time if some data packets are pre-scheduled and pre-stored into the cache of cloudlet if UE is switching from the previous Fog-RAN to the serving Fog-RAN. To illustrate the performance achievement, the mathematical analysis and simulation results are examined in terms of the total transmission time, the

A Mobility Management Using Follow-Me Cloud-Cloudlet in Fog-Computing-Based RANs for Smart Cities

Directory of Open Access Journals (Sweden)

Yuh-Shyan Chen

2018-02-01

Full Text Available Mobility management for supporting the location tracking and location-based service (LBS is an important issue of smart city by providing the means for the smooth transportation of people and goods. The mobility is useful to contribute the innovation in both public and private transportation infrastructures for smart cities. With the assistance of edge/fog computing, this paper presents a fully new mobility management using the proposed follow-me cloud-cloudlet (FMCL approach in fog-computing-based radio access networks (Fog-RANs for smart cities. The proposed follow-me cloud-cloudlet approach is an integration strategy of follow-me cloud (FMC and follow-me edge (FME (or called cloudlet. A user equipment (UE receives the data, transmitted from original cloud, into the original edge cloud before the handover operation. After the handover operation, an UE searches for a new cloud, called as a migrated cloud, and a new edge cloud, called as a migrated edge cloud near to UE, where the remaining data is migrated from the original cloud to the migrated cloud and all the remaining data are received in the new edge cloud. Existing FMC results do not have the property of the VM migration between cloudlets for the purpose of reducing the transmission latency, and existing FME results do not keep the property of the service migration between data centers for reducing the transmission latency. Our proposed FMCL approach can simultaneously keep the VM migration between cloudlets and service migration between data centers to significantly reduce the transmission latency. The new proposed mobility management using FMCL approach aims to reduce the total transmission time if some data packets are pre-scheduled and pre-stored into the cache of cloudlet if UE is switching from the previous Fog-RAN to the serving Fog-RAN. To illustrate the performance achievement, the mathematical analysis and simulation results are examined in terms of the total transmission time

Activation of mPTP-dependent mitochondrial apoptosis pathway by a novel pan HDAC inhibitor resminostat in hepatocellular carcinoma cells

Energy Technology Data Exchange (ETDEWEB)

Fu, Meili [Department of Infectious Disease, Linyi People’s Hospital, Linyi (China); Shi, Wenhong [Department of Radiotherapy, Linyi Tumor Hospital, Linyi (China); Li, Zhengling [Department of Nursing, Tengzhou Central People’s Hospital, Tengzhou (China); Liu, Haiyan, E-mail: liuhaiyanlinyi5@sina.com [Department of Nursing, Linyi People’s Hospital, No. 27 Jiefang Road, Linyi 276000, Shandong (China)

2016-09-02

Over-expression and aberrant activation of histone deacetylases (HDACs) are often associated with poor prognosis of hepatocellular carcinoma (HCC). Here, we evaluated the potential anti-hepatocellular carcinoma (HCC) cell activity by resminostat, a novel pan HDAC inhibitor (HDACi). We demonstrated that resminostat induced potent cytotoxic and anti-proliferative activity against established HCC cell lines (HepG2, HepB3, SMMC-7721) and patient-derived primary HCC cells. Further, resminostat treatment in HCC cells activated mitochondrial permeability transition pore (mPTP)-dependent apoptosis pathway, which was evidenced by physical association of cyclophilin-D and adenine nucleotide translocator 1 (ANT-1), mitochondrial depolarization, cytochrome C release and caspase-9 activation. Intriguingly, the mPTP blockers (sanglifehrin A and cyclosporine A), shRNA knockdown of cyclophilin-D or the caspase-9 inhibitor dramatically attenuated resminostat-induced HCC cell apoptosis and cytotoxicity. Reversely, HCC cells with exogenous cyclophilin-D over-expression were hyper-sensitive to resminostat. Intriguingly, a low concentration of resminostat remarkably potentiated sorafenib-induced mitochondrial apoptosis pathway activation, leading to a profound cytotoxicity in HCC cells. The results of this preclinical study indicate that resminostat (or plus sorafenib) could be further investigated as a valuable anti-HCC strategy. - Highlights: • Resminostat inhibits human HCC cell survival and proliferation. • Resminostat activates mPTP-dependent mitochondrial apoptosis pathway in HCC cells. • Resminostat potentiates sorafenib-induced mitochondrial apoptosis pathway activation. • mPTP or caspase-9 inhibition attenuates apoptosis by resminostat or plus sorafenib.

Aripiprazole and Haloperidol Activate GSK3β-Dependent Signalling Pathway Differentially in Various Brain Regions of Rats.

Science.gov (United States)

Pan, Bo; Huang, Xu-Feng; Deng, Chao

2016-03-28

Aripiprazole, a dopamine D₂ receptor (D₂R) partial agonist, possesses a unique clinical profile. Glycogen synthase kinase 3β (GSK3β)-dependent signalling pathways have been implicated in the pathophysiology of schizophrenia and antipsychotic drug actions. The present study examined whether aripiprazole differentially affects the GSK3β-dependent signalling pathways in the prefrontal cortex (PFC), nucleus accumbens (NAc), and caudate putamen (CPu), in comparison with haloperidol (a D₂R antagonist) and bifeprunox (a D₂R partial agonist). Rats were orally administrated aripiprazole (0.75 mg/kg), bifeprunox (0.8 mg/kg), haloperidol (0.1 mg/kg) or vehicle three times per day for one week. The levels of protein kinase B (Akt), p-Akt, GSK3β, p-GSK3β, dishevelled (Dvl)-3, and β-catenin were measured by Western Blots. Aripiprazole increased GSK3β phosphorylation in the PFC and NAc, respectively, while haloperidol elevated it in the NAc only. However, Akt activity was not changed by any of these drugs. Additionally, both aripiprazole and haloperidol, but not bifeprunox, increased the expression of Dvl-3 and β-catenin in the NAc. The present study suggests that activation of GSK3β phosphorylation in the PFC and NAc may be involved in the clinical profile of aripiprazole; additionally, aripiprazole can increase GSK3β phosphorylation via the Dvl-GSK3β-β-catenin signalling pathway in the NAc, probably due to its relatively low intrinsic activity at D₂Rs.

Regulation of c–myc expression by IFN–γ through Stat1-dependent and -independent pathways

Science.gov (United States)

Ramana, Chilakamarti V.; Grammatikakis, Nicholas; Chernov, Mikhail; Nguyen, Hannah; Goh, Kee Chuan; Williams, Bryan R.G.; Stark, George R.

2000-01-01

Interferons (IFNs) inhibit cell growth in a Stat1-dependent fashion that involves regulation of c–myc expression. IFN–γ suppresses c–myc in wild-type mouse embryo fibroblasts, but not in Stat1-null cells, where IFNs induce c–myc mRNA rapidly and transiently, thus revealing a novel signaling pathway. Both tyrosine and serine phosphorylation of Stat1 are required for suppression. Induced expression of c–myc is likely to contribute to the proliferation of Stat1-null cells in response to IFNs. IFNs also suppress platelet-derived growth factor (PDGF)-induced c–myc expression in wild-type but not in Stat1-null cells. A gamma-activated sequence element in the promoter is necessary but not sufficient to suppress c–myc expression in wild-type cells. In PKR-null cells, the phosphorylation of Stat1 on Ser727 and transactivation are both defective, and c–myc mRNA is induced, not suppressed, in response to IFN–γ. A role for Raf–1 in the Stat1-independent pathway is revealed by studies with geldanamycin, an HSP90-specific inhibitor, and by expression of a mutant of p50cdc37 that is unable to recruit HSP90 to the Raf–1 complex. Both agents abrogated the IFN–γ-dependent induction of c–myc expression in Stat1-null cells. PMID:10637230

Nobiletin Stimulates Chloride Secretion in Human Bronchial Epithelia via a cAMP/PKA-Dependent Pathway

Directory of Open Access Journals (Sweden)

Yuan Hao

2015-08-01

Full Text Available Background/Aims: Nobiletin, a citrus flavonoid isolated from tangerines, alters ion transport functions in intestinal epithelia, and has antagonistic effects on eosinophilic airway inflammation of asthmatic rats. The present study examined the effects of nobiletin on basal short-circuit current (ISC in a human bronchial epithelial cell line (16HBE14o-, and characterized the signal transduction pathways that allowed nobiletin to regulate electrolyte transport. Methods: The ISC measurement technique was used for transepithelial electrical measurements. Intracellular calcium ([Ca2+]i and cAMP were also quantified. Results: Nobiletin stimulated a concentration-dependent increase in ISC, which was due to Cl- secretion. The increase in ISC was inhibited by a cystic fibrosis transmembrane conductance regulator inhibitor (CFTRinh-172, but not by 4,4'-diisothiocyano-stilbene-2,2'-disulphonic acid (DIDS, Chromanol 293B, clotrimazole, or TRAM-34. Nobiletin-stimulated ISC was also sensitive to a protein kinase A (PKA inhibitor, H89, and an adenylate cyclase inhibitor, MDL-12330A. Nobiletin could not stimulate any increase in ISC in a cystic fibrosis (CF cell line, CFBE41o-, which lacked a functional CFTR. Nobiletin stimulated a real-time increase in cAMP, but not [Ca2+]i. Conclusion: Nobiletin stimulated transepithelial Cl- secretion across human bronchial epithelia. The mechanisms involved activation of adenylate cyclase- and cAMP/PKA-dependent pathways, leading to activation of apical CFTR Cl- channels.

RANS-based CFD simulations of sodium fast reactor wire-wrapped pin bundles

International Nuclear Information System (INIS)

Pointer, W. D.; Thomas, J.; Fanning, T.; Fischer, P.; Siegel, A.; Smith, J.; Tokuhiro, A.

2009-01-01

In response to recent renewed interest in the development of advanced fast reactors, an effort is underway to develop a high-performance computational multi-physics simulation suite for the design and safety analysis of sodium cooled fast reactors. Within the multi-resolution thermal-hydraulics simulation component of this framework, high-resolution spectral large eddy simulation methods are used to improve turbulence models from coarser resolution Reynolds-averaged Navier-Stokes methods, and in turn, that data is used to improve or extend correlations used in traditional sub-channel tools. These ongoing studies provide the foundation for the development of the intermediate RANS-based resolution level. Prior work has focused on the benchmarking of flow field predictions on in 7-pin, 19-pin, and 37-pin fuel assemblies. The present work extends these studies to 217-pin assemblies in support of initial efforts to benchmark heat transfer predictions using the RANS models against conventional sub-channel models. In an effort to reduce the number of computational cells required to describe a 217-pin geometry, the effects of simplification of the geometric description of the contact point between the wire and the pin are investigated. The advantages of using polyhedral-based meshing methods rather than trimmed cell meshing methods have been demonstrated, and the effects of changes in axial mesh resolution in these meshes have been investigated. Results show that the geometric simplification has little impact on predicted flow fields, as does the use of a polyhedral mesh of comparable mesh density in place of the original trimmed cell mesh. While reducing axial mesh density has a notable impact on the velocity field, reducing predicted exchange velocities between adjacent subchannels by as much 25%, the impact on predicted temperature fields is negligible. (authors)

OTN Transport of Baseband Radio Serial Protocols in C-RAN Architecture for Mobile Network Applications

OpenAIRE

Checko, Aleksandra; Kardaras, Georgios; Lanzani, Christian Fabio Alessandro; Temple, Dan; Mathiasen, Carsten; Pedersen, Lars A.; Klaps, Bert

2014-01-01

This white paper presents a proof of concept implementation of digital baseband radio data transport over Optical Transport Network (OTN) compliant to 3GPP Long Term Evolution – Advanced (LTE-A) standard enabling Cloud Radio Access Network (C-RAN) architecture. The transport between the baseband module and a remote radio module is compliant to Common Public Radio Interface (CPRI) and to the OBSAI reference point 3 - 01 (RP3-01) interface protocols, respectively. The purpose is to demonstrate ...

Spalart–Allmaras model apparent transition and RANS simulations of laminar separation bubbles on airfoils

International Nuclear Information System (INIS)

Crivellini, Andrea; D’Alessandro, Valerio

2014-01-01

Highlights: • RANS simulation of laminar separation bubbles. • Spalart–Allamaras unexpected capability. • Straightforward implementation of our SA modifications. • Applications of a high order DG incompressible solver. - Abstract: The present paper deals with the Reynolds Averaged Navier–Stokes (RANS) simulation of Laminar Separation Bubble (LSB). This phenomenon is of large interest in several engineering fields, such as the study of wind turbines, unmanned aerial vehicles (UAV) and micro-air vehicles (MAV) characterized by a low operating Reynolds number. In such contexts a laminar boundary layer separation followed by a turbulent transition and afterwards by a turbulent reattachment may appear in the flow-field. The main novelty of this work is that an almost standard Spalart–Allmaras (SA) model, without additional equations for transition modeling, was successfully employed. The result achieved is very surprising being the model not developed for this purpose, but for fully-turbulent flows or for cases with imposed transition location. This result is of large interest, since the SA model is widely used in commercial, open-source and research codes. However, our approach cannot be advocated to predict natural transition within an attached boundary layer, indeed it is only able to deal with transitions triggered by a separated flow. The reliability and accuracy of our approach are here proved computing, by means of a high-order Discontinuous Galerkin (DG) incompressible solver, the flow-field over two airfoils at different flow regimes showing the formation of a LSB

Non-classical crystallization of thin films and nanostructures in CVD and PVD processes

CERN Document Server

Hwang, Nong Moon

2016-01-01

This book provides a comprehensive introduction to a recently-developed approach to the growth mechanism of thin films and nanostructures via chemical vapour deposition (CVD). Starting from the underlying principles of the low pressure synthesis of diamond films, it is shown that diamond growth occurs not by individual atoms but by charged nanoparticles. This newly-discovered growth mechanism turns out to be general to many CVD and some physical vapor deposition (PVD) processes. This non-classical crystallization is a new paradigm of crystal growth, with active research taking place on growth in solution, especially in biomineralization processes. Established understanding of the growth of thin films and nanostructures is based around processes involving individual atoms or molecules. According to the author’s research over the last two decades, however, the generation of charged gas phase nuclei is shown to be the rule rather than the exception in the CVD process, and charged gas phase nuclei are actively ...

The aPKC-CBP Pathway Regulates Adult Hippocampal Neurogenesis in an Age-Dependent Manner

Directory of Open Access Journals (Sweden)

Ayden Gouveia

2016-10-01

Full Text Available While epigenetic modifications have emerged as attractive substrates to integrate environmental changes into the determination of cell identity and function, specific signals that directly activate these epigenetic modifications remain unknown. Here, we examine the role of atypical protein kinase C (aPKC-mediated Ser436 phosphorylation of CBP, a histone acetyltransferase, in adult hippocampal neurogenesis and memory. Using a knockin mouse strain (CbpS436A in which the aPKC-CBP pathway is deficient, we observe impaired hippocampal neuronal differentiation, maturation, and memory and diminished binding of CBP to CREB in 6-month-old CbpS436A mice, but not at 3 months of age. Importantly, elevation of CREB activity rescues these deficits, and CREB activity is reduced whereas aPKC activity is increased in the murine hippocampus as they age from 3 to 6 months regardless of genotype. Thus, the aPKC-CBP pathway is a homeostatic compensatory mechanism that modulates hippocampal neurogenesis and memory in an age-dependent manner in response to reduced CREB activity.

CFD RANS Simulations on a Generic Conventional Scale Model Submarine: Comparison between Fluent and OpenFOAM

Science.gov (United States)

2015-09-01

UNCLASSIFIED UNCLASSIFIED CFD RANS Simulations on a Generic Conventional Scale Model Submarine: Comparison between Fluent and OpenFOAM ... OpenFOAM to replace some of the Fluent simulations. The fidelity of the Fluent code has been carefully validated, but the accuracy of parts of the... OpenFOAM code have not been so extensively tested. To test the accuracy of the OpenFOAM software, CFD simulations have been performed on the DSTO

Investigation on hydrodynamic performance of a marine propeller in oblique flow by RANS computations

Directory of Open Access Journals (Sweden)

Jianxi Yao

2015-01-01

Full Text Available This paper presents a numerical study on investigating on hydrodynamic characteristics of a marine propeller in oblique flow. The study is achieved by RANS simulations on an open source platform - OpenFOAM. A sliding grid approach is applied to compute the rotating motion of the propeller. Total force and moment acting on blades, as well as average force distributions in one revolution on propeller disk, are obtained for 70 cases of com- binations of advance ratios and oblique angles. The computed results are compared with available experimental data and discussed.

Thrombin induces rapid PAR1-mediated non-classical FGF1 release

International Nuclear Information System (INIS)

Duarte, Maria; Kolev, Vihren; Soldi, Raffaella; Kirov, Alexander; Graziani, Irene; Oliveira, Silvia Marta; Kacer, Doreen; Friesel, Robert; Maciag, Thomas; Prudovsky, Igor

2006-01-01

Thrombin induces cell proliferation and migration during vascular injury. We report that thrombin rapidly stimulated expression and release of the pro-angiogenic polypeptide fibroblast growth factor 1 (FGF1). Thrombin failed to induce FGF1 release from protease-activated receptor 1 (PAR1) null fibroblasts, indicating that this effect was dependent on PAR1. Similarly to thrombin, FGF1 expression and release were induced by TRAP, a specific oligopeptide agonist of PAR1. These results identify a novel aspect of the crosstalk between FGF and thrombin signaling pathways which both play important roles in tissue repair and angiogenesis

Hydrogen peroxide induces activation of insulin signaling pathway via AMP-dependent kinase in podocytes

Energy Technology Data Exchange (ETDEWEB)

Piwkowska, Agnieszka, E-mail: apiwkowska@cmdik.pan.pl [Mossakowski Medical Research Centre, Polish Academy of Sciences, Laboratory of Molecular and Cellular Nephrology, Gdansk (Poland); Rogacka, Dorota; Angielski, Stefan [Mossakowski Medical Research Centre, Polish Academy of Sciences, Laboratory of Molecular and Cellular Nephrology, Gdansk (Poland); Jankowski, Maciej [Mossakowski Medical Research Centre, Polish Academy of Sciences, Laboratory of Molecular and Cellular Nephrology, Gdansk (Poland); Medical University of Gdansk, Department of Therapy Monitoring and Pharmacogenetics (Poland)

2012-11-09

Highlights: Black-Right-Pointing-Pointer H{sub 2}O{sub 2} activates the insulin signaling pathway and glucose uptake in podocytes. Black-Right-Pointing-Pointer H{sub 2}O{sub 2} induces time-dependent changes in AMPK phosphorylation. Black-Right-Pointing-Pointer H{sub 2}O{sub 2} enhances insulin signaling pathways via AMPK activation. Black-Right-Pointing-Pointer H{sub 2}O{sub 2} stimulation of glucose uptake is AMPK-dependent. -- Abstract: Podocytes are cells that form the glomerular filtration barrier in the kidney. Insulin signaling in podocytes is critical for normal kidney function. Insulin signaling is regulated by oxidative stress and intracellular energy levels. We cultured rat podocytes to investigate the effects of hydrogen peroxide (H{sub 2}O{sub 2}) on the phosphorylation of proximal and distal elements of insulin signaling. We also investigated H{sub 2}O{sub 2}-induced intracellular changes in the distribution of protein kinase B (Akt). Western blots showed that H{sub 2}O{sub 2} (100 {mu}M) induced rapid, transient phosphorylation of the insulin receptor (IR), the IR substrate-1 (IRS1), and Akt with peak activities at 5 min ({Delta} 183%, P < 0.05), 3 min ({Delta} 414%, P < 0.05), and 10 min ({Delta} 35%, P < 0.05), respectively. Immunostaining cells with an Akt-specific antibody showed increased intensity at the plasma membrane after treatment with H{sub 2}O{sub 2}>. Furthermore, H{sub 2}O{sub 2} inhibited phosphorylation of the phosphatase and tensin homologue (PTEN; peak activity at 10 min; {Delta} -32%, P < 0.05) and stimulated phosphorylation of the AMP-dependent kinase alpha subunit (AMPK{alpha}; 78% at 3 min and 244% at 10 min). The stimulation of AMPK was abolished with an AMPK inhibitor, Compound C (100 {mu}M, 2 h). Moreover, Compound C significantly reduced the effect of H{sub 2}O{sub 2} on IR phosphorylation by about 40% (from 2.07 {+-} 0.28 to 1.28 {+-} 0.12, P < 0.05). In addition, H{sub 2}O{sub 2} increased glucose uptake in podocytes

Performance evaluation of RANS-based turbulence models in simulating a honeycomb heat sink

Science.gov (United States)

Subasi, Abdussamet; Ozsipahi, Mustafa; Sahin, Bayram; Gunes, Hasan

2017-07-01

As well-known, there is not a universal turbulence model that can be used to model all engineering problems. There are specific applications for each turbulence model that make it appropriate to use, and it is vital to select an appropriate model and wall function combination that matches the physics of the problem considered. Therefore, in this study, performance of six well-known Reynolds-Averaged Navier-Stokes ( RANS) based turbulence models which are the Standard k {{-}} ɛ, the Renormalized Group k- ɛ, the Realizable k- ɛ, the Reynolds Stress Model, the k- ω and the Shear Stress Transport k- ω and accompanying wall functions which are the standard, the non-equilibrium and the enhanced are evaluated via 3D simulation of a honeycomb heat sink. The CutCell method is used to generate grid for the part including heat sink called test section while a hexahedral mesh is employed to discretize to inlet and outlet sections. A grid convergence study is conducted for verification process while experimental data and well-known correlations are used to validate the numerical results. Prediction of pressure drop along the test section, mean base plate temperature of the heat sink and temperature at the test section outlet are regarded as a measure of the performance of employed models and wall functions. The results indicate that selection of turbulence models and wall functions has a great influence on the results and, therefore, need to be selected carefully. Hydraulic and thermal characteristics of the honeycomb heat sink can be determined in a reasonable accuracy using RANS- based turbulence models provided that a suitable turbulence model and wall function combination is selected.

Nonclassical dynamics of the methyl group in 1,1,1-triphenylethane. Evidence from powder 1H NMR spectra

KAUST Repository

Osior, Agnieszka

2017-03-14

According to the damped quantum rotation (DQR) theory, hindered rotation of methyl groups, evidenced in nuclear magnetic resonance (NMR) line shapes, is a nonclassical process. It comprises a number of quantum-rate processes measured by two different quantum-rate constants. The classical jump model employing only one rate constant is reproduced if these quantum constants happen to be equal. The values of their ratio, or the nonclassicallity coefficient, determined hitherto from NMR spectra of single crystals and solutions range from about 1.20 to 1.30 in the latter case to above 5.0 in the former, with the value of 1 corresponding to the jump model. Presently, first systematic investigations of the DQR effects in wide-line NMR spectra of a powder sample are reported. For 1,1,1-triphenylethane deuterated in the aromatic positions, the relevant line-shape effects were monitored in the range 99–121 K. The values of the nonclassicality coefficient dropping from 2.7 to 1.7 were evaluated in line shape fits to the experimental powder spectra from the range 99–108 K. At these temperatures, the fits with the conventional line-shape model are visibly inferior to the DQR fits. Using a theoretical model reported earlier, a semiquantitative interpretation of the DQR parameters evaluated from the spectra is given. It is shown that the DQR effects as such can be detected in wide-line NMR spectra of powdered samples, which are relatively facile to measure. However, a fully quantitative picture of these effects can only be obtained from the much more demanding experiments on single crystals.

Fipronil induces apoptosis through caspase-dependent mitochondrial pathways in Drosophila S2 cells.

Science.gov (United States)

Zhang, Baoyan; Xu, Zhiping; Zhang, Yixi; Shao, Xusheng; Xu, Xiaoyong; Cheng, Jiaogao; Li, Zhong

2015-03-01

Fipronil is the first phenylpyrazole insecticide widely used in controlling pests, including pyrethroid, organophosphate and carbamate insecticides. It is generally accepted that fipronil elicits neurotoxicity via interactions with GABA and glutamate receptors, although alternative mechanisms have recently been proposed. This study evaluates the genotoxicity of fipronil and its likely mode of action in Drosophila S2 cells, as an in vitro model. Fipronil administrated the concentration- and time-dependent S2 cell proliferation. Intracellular biochemical assays showed that fipronil-induced S2 cell apoptosis coincided with a decrease in the mitochondrial membrane potential and an increase reactive oxygen species generation, a significant decrease of Bcl-2 and DIAP1, and a marked augmentation of Cyt c and caspase-3. Because caspase-3 is the major executioner caspase downstream of caspase-9 in Drosophila, enzyme activity assays were used to determine the activities of caspase-3 and caspase-9. Our results indicated that fipronil effectively induced apoptosis in Drosophila S2 cells through caspase-dependent mitochondrial pathways. Copyright © 2015 Elsevier Inc. All rights reserved.

Chlorpromazine-induced hepatotoxicity during inflammation is mediated by TIRAP-dependent signaling pathway in mice

International Nuclear Information System (INIS)

Gandhi, Adarsh; Guo, Tao; Shah, Pranav; Moorthy, Bhagavatula; Ghose, Romi

2013-01-01

Inflammation is a major component of idiosyncratic adverse drug reactions (IADRs). To understand the molecular mechanism of inflammation-mediated IADRs, we determined the role of the Toll-like receptor (TLR) signaling pathway in idiosyncratic hepatotoxicity of the anti-psychotic drug, chlorpromazine (CPZ). Activation of TLRs recruits the first adaptor protein, Toll-interleukin 1 receptor domain containing adaptor protein (TIRAP) to the TIR domain of TLRs leading to the activation of the downstream kinase, c-Jun-N-terminal kinase (JNK). Prolonged activation of JNK leads to cell-death. We hypothesized that activation of TLR2 by lipoteichoic acid (LTA) or TLR4 by lipopolysaccharide (LPS) will augment the hepatotoxicity of CPZ by TIRAP-dependent mechanism involving prolonged activation of JNK. Adult male C57BL/6, TIRAP +/+ and TIRAP −/− mice were pretreated with saline, LPS (2 mg/kg) or LTA (6 mg/kg) for 30 min or 16 h followed by CPZ (5 mg/kg) or saline (vehicle) up to 24 h. We found that treatment of mice with CPZ in presence of LPS or LTA leads to ∼ 3–4 fold increase in serum ALT levels, a marked reduction in hepatic glycogen content, significant induction of serum tumor necrosis factor (TNF) α and prolonged JNK activation, compared to LPS or LTA alone. Similar results were observed in TIRAP +/+ mice, whereas the effects of LPS or LTA on CPZ-induced hepatotoxicity were attenuated in TIRAP −/− mice. For the first time, we show that inflammation-mediated hepatotoxicity of CPZ is dependent on TIRAP, and involves prolonged JNK activation in vivo. Thus, TIRAP-dependent pathways may be targeted to predict and prevent inflammation-mediated IADRs. -- Highlights: ► Inflammation augments the toxicity of an idiosyncratic hepatotoxin chlorpromazine. ► Activation of Toll-like receptors by LPS or LTA induces chlorpromazine toxicity. ► Sustained stress kinase (JNK) activation is associated with chlorpromazine toxicity. ► These studies provide novel mechanistic

Chlorpromazine-induced hepatotoxicity during inflammation is mediated by TIRAP-dependent signaling pathway in mice

Energy Technology Data Exchange (ETDEWEB)

Gandhi, Adarsh, E-mail: adarsh.gandhi@nih.gov [University of Houston, Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, 1441 Moursund Street, Room 517, Houston, TX 77030 (United States); Guo, Tao, E-mail: tguo4@jhu.edu [University of Houston, Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, 1441 Moursund Street, Room 517, Houston, TX 77030 (United States); Shah, Pranav [University of Houston, Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, 1441 Moursund Street, Room 517, Houston, TX 77030 (United States); Moorthy, Bhagavatula [Baylor College of Medicine, Department of Pediatrics, 1102 Bates Avenue, Suite 530, Houston, TX 77030 (United States); Ghose, Romi, E-mail: rghose@uh.edu [University of Houston, Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, 1441 Moursund Street, Room 517, Houston, TX 77030 (United States)

2013-02-01

Inflammation is a major component of idiosyncratic adverse drug reactions (IADRs). To understand the molecular mechanism of inflammation-mediated IADRs, we determined the role of the Toll-like receptor (TLR) signaling pathway in idiosyncratic hepatotoxicity of the anti-psychotic drug, chlorpromazine (CPZ). Activation of TLRs recruits the first adaptor protein, Toll-interleukin 1 receptor domain containing adaptor protein (TIRAP) to the TIR domain of TLRs leading to the activation of the downstream kinase, c-Jun-N-terminal kinase (JNK). Prolonged activation of JNK leads to cell-death. We hypothesized that activation of TLR2 by lipoteichoic acid (LTA) or TLR4 by lipopolysaccharide (LPS) will augment the hepatotoxicity of CPZ by TIRAP-dependent mechanism involving prolonged activation of JNK. Adult male C57BL/6, TIRAP{sup +/+} and TIRAP{sup −/−} mice were pretreated with saline, LPS (2 mg/kg) or LTA (6 mg/kg) for 30 min or 16 h followed by CPZ (5 mg/kg) or saline (vehicle) up to 24 h. We found that treatment of mice with CPZ in presence of LPS or LTA leads to ∼ 3–4 fold increase in serum ALT levels, a marked reduction in hepatic glycogen content, significant induction of serum tumor necrosis factor (TNF) α and prolonged JNK activation, compared to LPS or LTA alone. Similar results were observed in TIRAP{sup +/+} mice, whereas the effects of LPS or LTA on CPZ-induced hepatotoxicity were attenuated in TIRAP{sup −/−} mice. For the first time, we show that inflammation-mediated hepatotoxicity of CPZ is dependent on TIRAP, and involves prolonged JNK activation in vivo. Thus, TIRAP-dependent pathways may be targeted to predict and prevent inflammation-mediated IADRs. -- Highlights: ► Inflammation augments the toxicity of an idiosyncratic hepatotoxin chlorpromazine. ► Activation of Toll-like receptors by LPS or LTA induces chlorpromazine toxicity. ► Sustained stress kinase (JNK) activation is associated with chlorpromazine toxicity. ► These studies

Book Review: A History of the Czechoslovak Ocean Shipping Company, 1948–1989: How a Small, Landlocked Country Ran Maritime Business During the Cold War

DEFF Research Database (Denmark)

Taudal Poulsen, René

2016-01-01

Review of: Lenka Krátká: A History of the Czechoslovak Ocean Shipping Company, 1948–1989: How a Small, Landlocked Country Ran Maritime Business During the Cold War. Stuttgart: Ibidem Verlag, 2015. x + 271 pp., tables, notes, bibliography. ISBN: 978-3-8382-0666-0, £23.90 (pbk).......Review of: Lenka Krátká: A History of the Czechoslovak Ocean Shipping Company, 1948–1989: How a Small, Landlocked Country Ran Maritime Business During the Cold War. Stuttgart: Ibidem Verlag, 2015. x + 271 pp., tables, notes, bibliography. ISBN: 978-3-8382-0666-0, £23.90 (pbk)....

Numerical investigation of the vortex-induced vibration of an elastically mounted circular cylinder at high Reynolds number (Re = 104 and low mass ratio using the RANS code.

Directory of Open Access Journals (Sweden)

Niaz Bahadur Khan

Full Text Available This study numerically investigates the vortex-induced vibration (VIV of an elastically mounted rigid cylinder by using Reynolds-averaged Navier-Stokes (RANS equations with computational fluid dynamic (CFD tools. CFD analysis is performed for a fixed-cylinder case with Reynolds number (Re = 104 and for a cylinder that is free to oscillate in the transverse direction and possesses a low mass-damping ratio and Re = 104. Previously, similar studies have been performed with 3-dimensional and comparatively expensive turbulent models. In the current study, the capability and accuracy of the RANS model are validated, and the results of this model are compared with those of detached eddy simulation, direct numerical simulation, and large eddy simulation models. All three response branches and the maximum amplitude are well captured. The 2-dimensional case with the RANS shear-stress transport k-w model, which involves minimal computational cost, is reliable and appropriate for analyzing the characteristics of VIV.

Mixture Growth Models of RAN and RAS Row by Row: Insight into the Reading System at Work over Time

Science.gov (United States)

Amtmann, Dagmar; Abbott, Robert D.; Berninger, V. W.

2007-01-01

Children (n = 122) and adults (n = 200) with dyslexia completed rapid automatic naming (RAN) letters, rapid automatic switching (RAS) letters and numbers, executive function (inhibition, verbal fluency), and phonological working memory tasks. Typically developing 3rd (n = 117) and 5th (n = 103) graders completed the RAS task. Instead of analyzing…

Tendency towards the Self-Citation among Journals in Iran and Turkey / İran ve Türkiye Dergilerinde Kendine Atıf Yapma Eğilimleri

Directory of Open Access Journals (Sweden)

Mohammad Hossein Biglu

2007-10-01

Full Text Available AbstractThis paper investigates the trends of Impact Factors and self-citation rates of journals indexed in the JCR by two neighbouring countries Iran and Turkey for a period of five years (2000- 2005. All data extracted from the Journal Citation Reports – Science Edition (2000-2005. The study showed that the portion of Turkish journals entering data to the JCR data bank is two times higher than the portion of Iranian journals. From a total number of 6,088 journals in the JCR in 2005, 3 (0.05% were published in Iran and the same number of journals published in Turkey. The 6,088 journals in the JCR produced 847,114 articles, 159 (0.02% appeared in the Iranian journals and 352 (0.04% in the Turkish journals. Of the 22,353,992 citations in 2005, 214 (0.001% came from Iranian journals and 911 (0.004% came from Turkish journals.The self-citation tendency by Iranian journals has increased dramatically throughout the period of study, it reached from 8% self-citation rate in 2000 to 18% in 2005, an increase of 2.25 times, whereas the self-citation rate by Turkish journals showed a negative trend, its self-citation rate fell from 22% in 2002 to 15% in 2005. The Impact Factors of Turkish journals showed faster growth than the Iranian journals, the mean value of Impact Factor for Turkish journals in 2000 was 0.49 under than the mean value of Impact Factor for Iranian journals, but in 2005 the mean value of Impact Factor for Turkish journals stayed 0.14 higher than the mean value of Impact Factor for Iranian journalsÖzBu makale, iki komşu ülke, İran ve Türkiye tarafından 5 yıl (2000-2005 içinde üretilen yayınlardan JCR’de dizinlenen dergilerdeki kendine atıfları ve etki faktöründeki eğilimleri incelemektedir. Bütün veriler JCR-Science Edition (2000-2005’den alınmıştır. Çalışma, Türk dergilerinin İran dergilerinden iki kat fazla miktarda JCR’ye girdiğini göstermektedir. 2005 yılında JCR’de yer alan toplam 6

Licochalcone A induces apoptosis in KB human oral cancer cells via a caspase-dependent FasL signaling pathway.

Science.gov (United States)

Kim, Jae-Sung; Park, Mi-Ra; Lee, Sook-Young; Kim, Do Kyoung; Moon, Sung-Min; Kim, Chun Sung; Cho, Seung Sik; Yoon, Goo; Im, Hee-Jeong; You, Jae-Seek; Oh, Ji-Su; Kim, Su-Gwan

2014-02-01

Licochalcone A (Lico-A) is a natural phenol licorice compound with multiple bioactivities, including anti-inflammatory, anti-microbial, anti-fungal and osteogenesis-inducing properties. In the present study, we investigated the Lico-A-induced apoptotic effects and examined the associated apoptosis pathway in KB human oral cancer cells. Lico-A decreased the number of viable KB oral cancer cells. However, Lico-A did not have an effect on primary normal human oral keratinocytes. In addition, the IC50 value of Lico-A was determined to be ~50 µM following dose-dependent stimulation. KB oral cancer cells stimulated with Lico-A for 24 h showed chromatin condensation by DAPI staining, genomic DNA fragmentation by agarose gel electrophoresis and a gradually increased apoptotic cell population by FACS analysis. These data suggest that Lico-A induces apoptosis in KB oral cancer cells. Additionally, Lico‑A‑induced apoptosis in KB oral cancer cells was mediated by the expression of factor associated suicide ligand (FasL) and activated caspase-8 and -3 and poly(ADP-ribose) polymerase (PARP). Furthermore, in the KB oral cancer cells co-stimulation with a caspase inhibitor (Z-VAD-fmk) and Lico-A significantly abolished the apoptotic phenomena. Our findings demonstrated that Lico‑A-induced apoptosis in KB oral cancer cells involves the extrinsic apoptotic signaling pathway, which involves a caspase-dependent FasL-mediated death receptor pathway. Our data suggest that Lico-A be developed as a chemotherapeutic agent for the management of oral cancer.

Flow field analysis of a pentagonal-shaped bridge deck by unsteady RANS

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Md. Naimul Haque

2016-01-01

Full Text Available Long-span cable-stayed bridges are susceptible to dynamic wind effects due to their inherent flexibility. The fluid flow around the bridge deck should be well understood for the efficient design of an aerodynamically stable long-span bridge system. In this work, the aerodynamic features of a pentagonal-shaped bridge deck are explored numerically. The analytical results are compared with past experimental work to assess the capability of two-dimensional unsteady RANS simulation for predicting the aerodynamic features of this type of deck. The influence of the bottom plate slope on aerodynamic response and flow features was investigated. By varying the Reynolds number (2 × 104 to 20 × 104 the aerodynamic behavior at high wind speeds is clarified.

Synchronization challenges in packet-based Cloud-RAN fronthaul for mobile networks

DEFF Research Database (Denmark)

Checko, Aleksandra; Juul, Anders Christian; Christiansen, Henrik Lehrmann

2015-01-01

In this paper, we look at reusing existing packet-based network (e.g. Ethernet) to possibly decrease deployment costs of fronthaul Cloud Radio Access Network (C-RAN) network and cost of Baseband Unit (BBU) resources. The challenge of this solution is that it requires mobile traffic (until now...... transmitted over synchronous protocols) to traverse the asynchronous Ethernet without losing synchronization. We analyze synchronization requirements of mobile networks and present an overview of solutions that fulfill them in traditional mobile networks. Then we elaborate on challenges that packet-based...... fronthaul imposes. We analyze possible contributions to frequency and phase error. We verify the feasibility of using the IEEE 1588v2 also know as Precision Time Protocol (PTP) for providing accurate phase and frequency synchronization. The study is based on simulations made in OPNET modeler. Thereby we...

ORF73 LANA homologs of RRV and MneRV2 contain an extended RGG/RG-rich nuclear and nucleolar localization signal that interacts directly with importin β1 for non-classical nuclear import.

Science.gov (United States)

Howard, Kellie; Cherezova, Lidia; DeMaster, Laura K; Rose, Timothy M

2017-11-01

The latency-associated nuclear antigens (LANA) of KSHV and macaque RFHVMn, members of the RV1 rhadinovirus lineage, are closely related with conservation of complex nuclear localization signals (NLS) containing bipartite KR-rich motifs and RG-rich domains, which interact distinctly with importins α and ß1 for nuclear import via classical and non-classical pathways, respectively. RV1 LANAs are expressed in the nucleus of latently-infected cells where they inhibit replication and establish a dominant RV1 latency. Here we show that LANA homologs of macaque RRV and MneRV2 from the more distantly-related RV2 lineage, lack the KR-rich NLS, and instead have a large RG-rich NLS with multiple RG dipeptides and a conserved RGG motif. The RG-NLS interacts uniquely with importin β1, which mediates nuclear import and accumulation of RV2 LANA in the nucleolus. The alternative nuclear import and localization of RV2 LANA homologs may contribute to the dominant RV2 lytic replication phenotype. Copyright © 2017. Published by Elsevier Inc.

Voltage-gated potassium channels regulate calcium-dependent pathways involved in human T lymphocyte activation.

Science.gov (United States)

Lin, C S; Boltz, R C; Blake, J T; Nguyen, M; Talento, A; Fischer, P A; Springer, M S; Sigal, N H; Slaughter, R S; Garcia, M L

1993-03-01

The role that potassium channels play in human T lymphocyte activation has been investigated by using specific potassium channel probes. Charybdotoxin (ChTX), a blocker of small conductance Ca(2+)-activated potassium channels (PK,Ca) and voltage-gated potassium channels (PK,V) that are present in human T cells, inhibits the activation of these cells. ChTX blocks T cell activation induced by signals (e.g., anti-CD2, anti-CD3, ionomycin) that elicit a rise in intracellular calcium ([Ca2+]i) by preventing the elevation of [Ca2+]i in a dose-dependent manner. However, ChTX has no effect on the activation pathways (e.g., anti-CD28, interleukin 2 [IL-2]) that are independent of a rise in [Ca2+]i. In the former case, both proliferative response and lymphokine production (IL-2 and interferon gamma) are inhibited by ChTX. The inhibitory effect of ChTX can be demonstrated when added simultaneously, or up to 4 h after the addition of the stimulants. Since ChTX inhibits both PK,Ca and PK,V, we investigated which channel is responsible for these immunosuppressive effects with the use of two other peptides, noxiustoxin (NxTX) and margatoxin (MgTX), which are specific for PK,V. These studies demonstrate that, similar to ChTX, both NxTX and MgTX inhibit lymphokine production and the rise in [Ca2+]i. Taken together, these data provide evidence that blockade of PK,V affects the Ca(2+)-dependent pathways involved in T lymphocyte proliferation and lymphokine production by diminishing the rise in [Ca2+]i that occurs upon T cell activation.

Epstein-Barr virus associated modulation of Wnt pathway is not dependent on latent membrane protein-1.

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Natasha Webb

2008-09-01

Full Text Available Previous studies have indicated that Epstein-Barr virus (EBV can modulate the Wnt pathway in virus-infected cells and this effect is mediated by EBV-encoded oncogene latent membrane protein 1 (LMP1. Here we have reassessed the role of LMP1 in regulating the expression of various mediators of the canonical Wnt cascade. Contradicting the previous finding, we found that the levels of E-cadherin, beta-catenin, Glycogen Synthase Kinase 3ss (GSK3beta, axin and alpha-catenin were not affected by the expression of LMP1 sequences from normal B cells or nasopharyngeal carcinoma. Moreover, we also show that LMP1 expression had no detectable effect on the E-cadherin and beta-catenin interaction and did not induce transcriptional activation of beta-catenin. Taken together these studies demonstrate that EBV-mediated activation of Wnt pathway is not dependent on the expression of LMP1.

The nuclear import of ribosomal proteins is regulated by mTOR

Science.gov (United States)

Kazyken, Dubek; Kaz, Yelimbek; Kiyan, Vladimir; Zhylkibayev, Assylbek A.; Chen, Chien-Hung; Agarwal, Nitin K.; Sarbassov, Dos D.

2014-01-01

Mechanistic target of rapamycin (mTOR) is a central component of the essential signaling pathway that regulates cell growth and proliferation by controlling anabolic processes in cells. mTOR exists in two distinct mTOR complexes known as mTORC1 and mTORC2 that reside mostly in cytoplasm. In our study, the biochemical characterization of mTOR led to discovery of its novel localization on nuclear envelope where it associates with a critical regulator of nuclear import Ran Binding Protein 2 (RanBP2). We show that association of mTOR with RanBP2 is dependent on the mTOR kinase activity that regulates the nuclear import of ribosomal proteins. The mTOR kinase inhibitors within thirty minutes caused a substantial decrease of ribosomal proteins in the nuclear but not cytoplasmic fraction. Detection of a nuclear accumulation of the GFP-tagged ribosomal protein rpL7a also indicated its dependence on the mTOR kinase activity. The nuclear abundance of ribosomal proteins was not affected by inhibition of mTOR Complex 1 (mTORC1) by rapamycin or deficiency of mTORC2, suggesting a distinctive role of the nuclear envelope mTOR complex in the nuclear import. Thus, we identified that mTOR in association with RanBP2 mediates the active nuclear import of ribosomal proteins. PMID:25294810

Endothelium derived nitric oxide synthase negatively regulates the PDGF-survivin pathway during flow-dependent vascular remodeling.

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Jun Yu

Full Text Available Chronic alterations in blood flow initiate structural changes in vessel lumen caliber to normalize shear stress. The loss of endothelial derived nitric oxide synthase (eNOS in mice promotes abnormal flow dependent vascular remodeling, thus uncoupling mechanotransduction from adaptive vascular remodeling. However, the mechanisms of how the loss of eNOS promotes abnormal remodeling are not known. Here we show that abnormal flow-dependent remodeling in eNOS knockout mice (eNOS (-/- is associated with activation of the platelet derived growth factor (PDGF signaling pathway leading to the induction of the inhibitor of apoptosis, survivin. Interfering with PDGF signaling or survivin function corrects the abnormal remodeling seen in eNOS (-/- mice. Moreover, nitric oxide (NO negatively regulates PDGF driven survivin expression and cellular proliferation in cultured vascular smooth muscle cells. Collectively, our data suggests that eNOS negatively regulates the PDGF-survivin axis to maintain proportional flow-dependent luminal remodeling and vascular quiescence.

On Some Nonclassical Algebraic Properties of Interval-Valued Fuzzy Soft Sets

Science.gov (United States)

2014-01-01

Interval-valued fuzzy soft sets realize a hybrid soft computing model in a general framework. Both Molodtsov's soft sets and interval-valued fuzzy sets can be seen as special cases of interval-valued fuzzy soft sets. In this study, we first compare four different types of interval-valued fuzzy soft subsets and reveal the relations among them. Then we concentrate on investigating some nonclassical algebraic properties of interval-valued fuzzy soft sets under the soft product operations. We show that some fundamental algebraic properties including the commutative and associative laws do not hold in the conventional sense, but hold in weaker forms characterized in terms of the relation =L. We obtain a number of algebraic inequalities of interval-valued fuzzy soft sets characterized by interval-valued fuzzy soft inclusions. We also establish the weak idempotent law and the weak absorptive law of interval-valued fuzzy soft sets using interval-valued fuzzy soft J-equal relations. It is revealed that the soft product operations ∧ and ∨ of interval-valued fuzzy soft sets do not always have similar algebraic properties. Moreover, we find that only distributive inequalities described by the interval-valued fuzzy soft L-inclusions hold for interval-valued fuzzy soft sets. PMID:25143964

On Some Nonclassical Algebraic Properties of Interval-Valued Fuzzy Soft Sets

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Xiaoyan Liu

2014-01-01

Full Text Available Interval-valued fuzzy soft sets realize a hybrid soft computing model in a general framework. Both Molodtsov’s soft sets and interval-valued fuzzy sets can be seen as special cases of interval-valued fuzzy soft sets. In this study, we first compare four different types of interval-valued fuzzy soft subsets and reveal the relations among them. Then we concentrate on investigating some nonclassical algebraic properties of interval-valued fuzzy soft sets under the soft product operations. We show that some fundamental algebraic properties including the commutative and associative laws do not hold in the conventional sense, but hold in weaker forms characterized in terms of the relation =L. We obtain a number of algebraic inequalities of interval-valued fuzzy soft sets characterized by interval-valued fuzzy soft inclusions. We also establish the weak idempotent law and the weak absorptive law of interval-valued fuzzy soft sets using interval-valued fuzzy soft J-equal relations. It is revealed that the soft product operations ∧ and ∨ of interval-valued fuzzy soft sets do not always have similar algebraic properties. Moreover, we find that only distributive inequalities described by the interval-valued fuzzy soft L-inclusions hold for interval-valued fuzzy soft sets.

On some nonclassical algebraic properties of interval-valued fuzzy soft sets.

Science.gov (United States)

Liu, Xiaoyan; Feng, Feng; Zhang, Hui

2014-01-01

Interval-valued fuzzy soft sets realize a hybrid soft computing model in a general framework. Both Molodtsov's soft sets and interval-valued fuzzy sets can be seen as special cases of interval-valued fuzzy soft sets. In this study, we first compare four different types of interval-valued fuzzy soft subsets and reveal the relations among them. Then we concentrate on investigating some nonclassical algebraic properties of interval-valued fuzzy soft sets under the soft product operations. We show that some fundamental algebraic properties including the commutative and associative laws do not hold in the conventional sense, but hold in weaker forms characterized in terms of the relation = L . We obtain a number of algebraic inequalities of interval-valued fuzzy soft sets characterized by interval-valued fuzzy soft inclusions. We also establish the weak idempotent law and the weak absorptive law of interval-valued fuzzy soft sets using interval-valued fuzzy soft J-equal relations. It is revealed that the soft product operations ∧ and ∨ of interval-valued fuzzy soft sets do not always have similar algebraic properties. Moreover, we find that only distributive inequalities described by the interval-valued fuzzy soft L-inclusions hold for interval-valued fuzzy soft sets.

New perspectives for "non-classical" molecules: heavy [1.1.1]propellanes of group 14.

Science.gov (United States)

Nied, Dominik; Breher, Frank

2011-07-01

Heavy analogues of hydrocarbons intrigue chemists for a number of reasons, not least because they are often fundamentally different from their carbon counterparts and have remained a challenge for both experimentalists and theoreticians for a long time. The appealing properties of [1.1.1]propellanes of group 14 consisting of inverted tetrahedral bridgehead atoms can mainly be attributed to the particular bonding between the latter. More than 20 years after the first member of this family has been published, several contributions to this area have impressively extended the spectrum of these so-called main-group biradicaloids. Still in its infancy, further perspectives for these "non-classical" molecules are now arising. In this tutorial review, early findings and recent developments in this area are presented. Particular attention is drawn on the relationship of unusual structures and unusual reactivities of main-group element compounds in general and in particular of heavy propellane scaffolds of group 14.

The Defense Metabolite, Allyl Glucosinolate, Modulates Arabidopsis thaliana Biomass Dependent upon the Endogenous Glucosinolate Pathway.

Science.gov (United States)

Francisco, Marta; Joseph, Bindu; Caligagan, Hart; Li, Baohua; Corwin, Jason A; Lin, Catherine; Kerwin, Rachel; Burow, Meike; Kliebenstein, Daniel J

2016-01-01

Glucosinolates (GSLs) play an important role in plants as direct mediators of biotic and abiotic stress responses. Recent work is beginning to show that the GSLs can also inducing complex defense and growth networks. However, the physiological significance of these GSL-induced responses and the molecular mechanisms by which GSLs are sensed and/or modulate these responses are not understood. To identify these potential mechanisms within the plant and how they may relate to the endogenous GSLs, we tested the regulatory effect of exogenous allyl GSL application on growth and defense metabolism across sample of Arabidopsis thaliana accessions. We found that application of exogenous allyl GSL had the ability to initiate changes in plant biomass and accumulation of defense metabolites that genetically varied across accessions. This growth effect was related to the allyl GSL side-chain structure. Utilizing this natural variation and mutants in genes within the GSL pathway we could show that the link between allyl GSL and altered growth responses are dependent upon the function of known genes controlling the aliphatic GSL pathway.

Nitric oxide-sensitive guanylyl cyclase is differentially regulated by nuclear and non-nuclear estrogen pathways in anterior pituitary gland.

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Jimena P Cabilla

Full Text Available 17β-estradiol (E2 regulates hormonal release as well as proliferation and cell death in the pituitary. The main nitric oxide receptor, nitric oxide sensitive- or soluble guanylyl cyclase (sGC, is a heterodimer composed of two subunits, α and β, that catalyses cGMP formation. α1β1 is the most abundant and widely expressed heterodimer, showing the greater activity. Previously we have shown that E2 decreased sGC activity but exerts opposite effects on sGC subunits increasing α1 and decreasing β1 mRNA and protein levels. In the present work we investigate the mechanisms by which E2 differentially regulates sGC subunits' expression on rat anterior pituitary gland. Experiments were performed on primary cultures of anterior pituitary cells from adult female Wistar rats at random stages of estrous cycle. After 6 h of E2 treatment, α1 mRNA and protein expression is increased while β1 levels are down-regulated. E2 effects on sGC expression are partially dependent on de novo transcription while de novo translation is fully required. E2 treatment decreased HuR mRNA stabilization factor and increased AUF1 p37 mRNA destabilization factor. E2-elicited β1 mRNA decrease correlates with a mRNA destabilization environment in the anterior pituitary gland. On the other hand, after 6 h of treatment, E2-BSA (1 nM and E2-dendrimer conjugate (EDC, 1 nM were unable to modify α1 or β1 mRNA levels, showing that nuclear receptor is involved in E2 actions. However, at earlier times (3 h, 1 nM EDC causes a transient decrease of α1 in a PI3k-dependent fashion. Our results show for the first time that E2 is able to exert opposite actions in the anterior pituitary gland, depending on the activation of classical or non-classical pathways. Thus, E2 can also modify sGC expression through membrane-initiated signals bringing to light a new point of regulation in NO/sGC pathway.

Nitric oxide-sensitive guanylyl cyclase is differentially regulated by nuclear and non-nuclear estrogen pathways in anterior pituitary gland.

Science.gov (United States)

Cabilla, Jimena P; Nudler, Silvana I; Ronchetti, Sonia A; Quinteros, Fernanda A; Lasaga, Mercedes; Duvilanski, Beatriz H

2011-01-01

17β-estradiol (E2) regulates hormonal release as well as proliferation and cell death in the pituitary. The main nitric oxide receptor, nitric oxide sensitive- or soluble guanylyl cyclase (sGC), is a heterodimer composed of two subunits, α and β, that catalyses cGMP formation. α1β1 is the most abundant and widely expressed heterodimer, showing the greater activity. Previously we have shown that E2 decreased sGC activity but exerts opposite effects on sGC subunits increasing α1 and decreasing β1 mRNA and protein levels. In the present work we investigate the mechanisms by which E2 differentially regulates sGC subunits' expression on rat anterior pituitary gland. Experiments were performed on primary cultures of anterior pituitary cells from adult female Wistar rats at random stages of estrous cycle. After 6 h of E2 treatment, α1 mRNA and protein expression is increased while β1 levels are down-regulated. E2 effects on sGC expression are partially dependent on de novo transcription while de novo translation is fully required. E2 treatment decreased HuR mRNA stabilization factor and increased AUF1 p37 mRNA destabilization factor. E2-elicited β1 mRNA decrease correlates with a mRNA destabilization environment in the anterior pituitary gland. On the other hand, after 6 h of treatment, E2-BSA (1 nM) and E2-dendrimer conjugate (EDC, 1 nM) were unable to modify α1 or β1 mRNA levels, showing that nuclear receptor is involved in E2 actions. However, at earlier times (3 h), 1 nM EDC causes a transient decrease of α1 in a PI3k-dependent fashion. Our results show for the first time that E2 is able to exert opposite actions in the anterior pituitary gland, depending on the activation of classical or non-classical pathways. Thus, E2 can also modify sGC expression through membrane-initiated signals bringing to light a new point of regulation in NO/sGC pathway. © 2011 Cabilla et al.

Regulation of non-classical immune parameters in immune thrombocytopenic purpura mice by a spleen-invigorating, qi-replenishing and blood-containing formula

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Tiantian Li

2015-04-01

Conclusions: The SQBF had a similar effect to prednisone with regards to enhancing peripheral blood platelet counts in ITP mice. Furthermore, it decreased β-EP levels and increased VIP and SIgA, and protected the thymus. This shows that, on base of the brain-gut axis functions, some non-classical immune vascular active factors or neurotransmitters are also involved in immune responses, and also have relationship with the onset of ITP and bleeding and/or hemostasis. It needs further study to determine whether a change in these active factors is related to immediate hemostasis.

Anti-neuroinflammatory efficacy of the aldose reductase inhibitor FMHM via phospholipase C/protein kinase C-dependent NF-κB and MAPK pathways

Energy Technology Data Exchange (ETDEWEB)

Zeng, Ke-Wu [State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191 (China); Li, Jun [Modern Research Center for Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029 (China); Dong, Xin; Wang, Ying-Hong; Ma, Zhi-Zhong; Jiang, Yong; Jin, Hong-Wei [State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191 (China); Tu, Peng-Fei, E-mail: pengfeitu@vip.163.com [State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191 (China); Modern Research Center for Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029 (China)

2013-11-15

Aldose reductase (AR) has a key role in several inflammatory diseases: diabetes, cancer and cardiovascular diseases. Therefore, AR inhibition seems to be a useful strategy for anti-inflammation therapy. In the central nervous system (CNS), microglial over-activation is considered to be a central event in neuroinflammation. However, the effects of AR inhibition in CNS inflammation and its underlying mechanism of action remain unknown. In the present study, we found that FMHM (a naturally derived AR inhibitor from the roots of Polygala tricornis Gagnep.) showed potent anti-neuroinflammatory effects in vivo and in vitro by inhibiting microglial activation and expression of inflammatory mediators. Mechanistic studies showed that FMHM suppressed the activity of AR-dependent phospholipase C/protein kinase C signaling, which further resulted in downstream inactivation of the IκB kinase/IκB/nuclear factor-kappa B (NF-κB) inflammatory pathway. Therefore, AR inhibition-dependent NF-κB inactivation negatively regulated the transcription and expression of various inflammatory genes. AR inhibition by FMHM exerted neuroprotective effects in lipopolysaccharide-induced neuron–microglia co-cultures. These findings suggested that AR is a potential target for neuroinflammation inhibition and that FMHM could be an effective agent for treating or preventing neuroinflammatory diseases. - Highlights: • FMHM is a natural-derived aldose reductase (AR) inhibitor. • FMHM inhibits various neuroinflammatory mediator productions in vitro and in vivo. • FMHM inhibits neuroinflammation via aldose reductase/PLC/PKC-dependent NF-κB pathway. • FMHM inhibits neuroinflammation via aldose reductase/PLC/PKC-dependent MAPK pathway. • FMHM protects neurons against inflammatory injury in microglia-neuron co-cultures.

Lactobacillus casei triggers a TLR mediated RACK-1 dependent p38 MAPK pathway in Caenorhabditis elegans to resist Klebsiella pneumoniae infection.

Science.gov (United States)

Kamaladevi, Arumugam; Balamurugan, Krishnaswamy

2016-07-13

In the present study, the effect of Lactic Acid Bacteria (LAB) was investigated at the molecular level using the model organism Caenorhabditis elegans against Klebsiella pneumoniae. Out of the 13 LAB screened, Lactobacillus casei displayed excellent protective efficacy by prolonging the survival of K. pneumoniae-infected nematodes. Pretreatment with L. casei significantly decreased bacterial colonization and rescued K. pneumoniae-infected C. elegans from various physiological impairments. The concomitant upregulation of key immune genes that regulate the TLR, RACK-1 as well as the p38 MAPK pathway rather than the IIS and ERK pathway suggested that the plausible immunomodulatory mechanism of L. casei could be by triggering the TLR, RACK-1 and p38 MAPK pathway. Furthermore, the hyper-susceptibility of L. casei treated loss-of-function mutants of the tol-1, RACK-1 and p38 MAPK pathway (sek-1 and pmk-1) to K. pneumoniae infection and gene expression analysis suggested that L. casei triggered a TLR mediated RACK-1 dependent p38 MAPK pathway to increase host resistance and protect nematodes against K. pneumoniae infection.

Non-classical logic inverter coupling a ZnO nanowire-based Schottky barrier transistor and adjacent Schottky diode.

Science.gov (United States)

Hosseini Shokouh, Seyed Hossein; Raza, Syed Raza Ali; Lee, Hee Sung; Im, Seongil

2014-08-21

On a single ZnO nanowire (NW), we fabricated an inverter-type device comprising a Schottky diode (SD) and field-effect transistor (FET), aiming at 1-dimensional (1D) electronic circuits with low power consumption. The SD and adjacent FET worked respectively as the load and driver, so that voltage signals could be easily extracted as the output. In addition, NW FET with a transparent conducting oxide as top gate turned out to be very photosensitive, although ZnO NW SD was blind to visible light. Based on this, we could achieve an array of photo-inverter cells on one NW. Our non-classical inverter is regarded as quite practical for both logic and photo-sensing due to its performance as well as simple device configuration.

Influence of pump-field scattering on nonclassical-light generation in a photonic-band-gap nonlinear planar waveguide

International Nuclear Information System (INIS)

Perina, Jan Jr.; Sibilia, Concita; Tricca, Daniela; Bertolotti, Mario

2005-01-01

Optical parametric process occurring in a nonlinear planar waveguide can serve as a source of light with nonclassical properties. The properties of the generated fields are substantially modified by scattering of the nonlinearly interacting fields in a photonic-band-gap structure inside the waveguide. A general quantum model of linear operator amplitude corrections to the amplitude mean values and its numerical analysis provide conditions for efficient squeezed-light generation as well as generation of light with sub-Poissonian photon-number statistics. The destructive influence of phase mismatch of the nonlinear interaction can fully be compensated using a suitable photonic-band-gap structure inside the waveguide. Also an increase of the signal-to-noise ratio of the incident optical field can be reached in the waveguide

Licochalcone A induces apoptosis in KB human oral cancer cells via a caspase-dependent FasL signaling pathway

Science.gov (United States)

KIM, JAE-SUNG; PARK, MI-RA; LEE, SOOK-YOUNG; KIM, DO KYOUNG; MOON, SUNG-MIN; KIM, CHUN SUNG; CHO, SEUNG SIK; YOON, GOO; IM, HEE-JEONG; YOU, JAE-SEEK; OH, JI-SU; KIM, SU-GWAN

2014-01-01

Licochalcone A (Lico-A) is a natural phenol licorice compound with multiple bioactivities, including anti-inflammatory, anti-microbial, anti-fungal and osteogenesis-inducing properties. In the present study, we investigated the Lico-A-induced apoptotic effects and examined the associated apoptosis pathway in KB human oral cancer cells. Lico-A decreased the number of viable KB oral cancer cells. However, Lico-A did not have an effect on primary normal human oral keratinocytes. In addition, the IC50 value of Lico-A was determined to be ~50 μM following dose-dependent stimulation. KB oral cancer cells stimulated with Lico-A for 24 h showed chromatin condensation by DAPI staining, genomic DNA fragmentation by agarose gel electrophoresis and a gradually increased apoptotic cell population by FACS analysis. These data suggest that Lico-A induces apoptosis in KB oral cancer cells. Additionally, Lico-A-induced apoptosis in KB oral cancer cells was mediated by the expression of factor associated suicide ligand (FasL) and activated caspase-8 and −3 and poly(ADP-ribose) polymerase (PARP). Furthermore, in the KB oral cancer cells co-stimulation with a caspase inhibitor (Z-VAD-fmk) and Lico-A significantly abolished the apoptotic phenomena. Our findings demonstrated that Lico-A-induced apoptosis in KB oral cancer cells involves the extrinsic apoptotic signaling pathway, which involves a caspase-dependent FasL-mediated death receptor pathway. Our data suggest that Lico-A be developed as a chemotherapeutic agent for the management of oral cancer. PMID:24337492

Constitutive MHC class I molecules negatively regulate TLR-triggered inflammatory responses via the Fps-SHP-2 pathway.

Science.gov (United States)

Xu, Sheng; Liu, Xingguang; Bao, Yan; Zhu, Xuhui; Han, Chaofeng; Zhang, Peng; Zhang, Xuemin; Li, Weihua; Cao, Xuetao

2012-04-22

The molecular mechanisms that fine-tune Toll-like receptor (TLR)-triggered innate inflammatory responses remain to be fully elucidated. Major histocompatibility complex (MHC) molecules can mediate reverse signaling and have nonclassical functions. Here we found that constitutively expressed membrane MHC class I molecules attenuated TLR-triggered innate inflammatory responses via reverse signaling, which protected mice from sepsis. The intracellular domain of MHC class I molecules was phosphorylated by the kinase Src after TLR activation, then the tyrosine kinase Fps was recruited via its Src homology 2 domain to phosphorylated MHC class I molecules. This led to enhanced Fps activity and recruitment of the phosphatase SHP-2, which interfered with TLR signaling mediated by the signaling molecule TRAF6. Thus, constitutive MHC class I molecules engage in crosstalk with TLR signaling via the Fps-SHP-2 pathway and control TLR-triggered innate inflammatory responses.

BMAL1-dependent regulation of the mTOR signaling pathway delays aging.

Science.gov (United States)

Khapre, Rohini V; Kondratova, Anna A; Patel, Sonal; Dubrovsky, Yuliya; Wrobel, Michelle; Antoch, Marina P; Kondratov, Roman V

2014-01-01

The circadian clock, an internal time-keeping system, has been linked with control of aging, but molecular mechanisms of regulation are not known. BMAL1 is a transcriptional factor and core component of the circadian clock; BMAL1 deficiency is associated with premature aging and reduced lifespan. Here we report that activity of mammalian Target of Rapamycin Complex 1 (mTORC1) is increased upon BMAL1 deficiency both in vivo and in cell culture. Increased mTOR signaling is associated with accelerated aging; in accordance with that, treatment with the mTORC1 inhibitor rapamycin increased lifespan of Bmal1-/- mice by 50%. Our data suggest that BMAL1 is a negative regulator of mTORC1 signaling. We propose that the circadian clock controls the activity of the mTOR pathway through BMAL1-dependent mechanisms and this regulation is important for control of aging and metabolism.

The synthesis of [O-methyl-{sup 11}C]venlafaxine: a non-classical, fast-acting antidepressant

Energy Technology Data Exchange (ETDEWEB)

Gee, A.D.; Gjedde, A. [Aarhus Univ. Hospital, PET Center, Aarhus (Denmark); Smith, D.F. [Aarhus Univ. Psychiatric Hospital, Inst. for Biological Psychiatry, Risskov (Denmark)

1997-01-01

As part of our program to develop PET tracers for the 5-HT reuptake site, venlafaxine, a non-classical, fast-acting antidepressant, was selected as a candidate for labelling with {sup 11}C for in vivo evaluation. [O-methyl-{sup 11}C]venlafaxine was produced by the alkylation of O-desmethyl venlafaxine with [{sup 11}C]methyl iodide followed by HPLC purification and formulation. Radiochemically pure [O-methyl-{sup 11}C]venlafaxine was obtained in a 30 {+-} 5% decay corrected radiochemical yield and a specific activity > 50 GBq/{mu}mol(1.4 Ci/{mu}mol) at the end of synthesis. For a typical production starting with 46 GBq (1.3 Ci) [{sup 11}C]CO{sub 2}, 5.2 GBq (140 mCi) [O-methyl-{sup 11}C]venlafaxine was obtained as a sterile, formulated solution in a synthesis time of 30 min (counted from EOB). (Author).

Glucose-induced lipid deposition in goose primary hepatocytes is dependent on the PI3K-Akt-mTOR signaling pathway

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Han Chunchun

2016-01-01

Full Text Available Previously we showed that fatty liver formation in overfed geese was accompanied by PI3K-Akt-mTOR pathway activation and changes in plasma glucose concentrations. Here, we show that glucose acts in goose hepatocellular lipid metabolism through the PI3K-Akt-mTOR signaling pathway. We observed that glucose increased lipogenesis, decreased fatty acid oxidation and increased very low density lipoprotein triglyceride (VLDL-TG assembly and secretion. Co-treatment with glucose and inhibitors of the PI3K-Akt-mTOR pathway (LY294002, rapamycin, NVP-BEZ235 decreased the levels of factors involved in lipogenesis and increased the levels of factors involved in fatty acid oxidation and VLDL-TG assembly and secretion. These findings show that inhibition of the PI3K-Akt-mTOR pathway decreased glucose-induced lipogenesis, inhibited the downregulation of fatty acid oxidation by glucose and increased the upregulation of VLDL-TG assembly and secretion by glucose. The results presented herein provide further support for the role of the PI3K-Akt-mTOR pathway in lipid metabolism as we showed that in goose primary hepatocytes, glucose acts through the PI3K-Akt-mTOR-dependent pathway to stimulate lipid deposition by increasing lipogenesis and decreasing fatty acid oxidation and VLDL-TG assembly and secretion.

DNA damage tolerance pathway involving DNA polymerase ι and the tumor suppressor p53 regulates DNA replication fork progression.

Science.gov (United States)

Hampp, Stephanie; Kiessling, Tina; Buechle, Kerstin; Mansilla, Sabrina F; Thomale, Jürgen; Rall, Melanie; Ahn, Jinwoo; Pospiech, Helmut; Gottifredi, Vanesa; Wiesmüller, Lisa

2016-07-26

DNA damage tolerance facilitates the progression of replication forks that have encountered obstacles on the template strands. It involves either translesion DNA synthesis initiated by proliferating cell nuclear antigen monoubiquitination or less well-characterized fork reversal and template switch mechanisms. Herein, we characterize a novel tolerance pathway requiring the tumor suppressor p53, the translesion polymerase ι (POLι), the ubiquitin ligase Rad5-related helicase-like transcription factor (HLTF), and the SWI/SNF catalytic subunit (SNF2) translocase zinc finger ran-binding domain containing 3 (ZRANB3). This novel p53 activity is lost in the exonuclease-deficient but transcriptionally active p53(H115N) mutant. Wild-type p53, but not p53(H115N), associates with POLι in vivo. Strikingly, the concerted action of p53 and POLι decelerates nascent DNA elongation and promotes HLTF/ZRANB3-dependent recombination during unperturbed DNA replication. Particularly after cross-linker-induced replication stress, p53 and POLι also act together to promote meiotic recombination enzyme 11 (MRE11)-dependent accumulation of (phospho-)replication protein A (RPA)-coated ssDNA. These results implicate a direct role of p53 in the processing of replication forks encountering obstacles on the template strand. Our findings define an unprecedented function of p53 and POLι in the DNA damage response to endogenous or exogenous replication stress.

A second component of the SltA-dependent cation tolerance pathway in Aspergillus nidulans.

Science.gov (United States)

Mellado, Laura; Calcagno-Pizarelli, Ana Maria; Lockington, Robin A; Cortese, Marc S; Kelly, Joan M; Arst, Herbert N; Espeso, Eduardo A

2015-09-01

The transcriptional response to alkali metal cation stress is mediated by the zinc finger transcription factor SltA in Aspergillus nidulans and probably in other fungi of the pezizomycotina subphylum. A second component of this pathway has been identified and characterized. SltB is a 1272 amino acid protein with at least two putative functional domains, a pseudo-kinase and a serine-endoprotease, involved in signaling to the transcription factor SltA. Absence of SltB activity results in nearly identical phenotypes to those observed for a null sltA mutant. Hypersensitivity to a variety of monovalent and divalent cations, and to medium alkalinization are among the phenotypes exhibited by a null sltB mutant. Calcium homeostasis is an exception and this cation improves growth of sltΔ mutants. Moreover, loss of kinase HalA in conjunction with loss-of-function sltA or sltB mutations leads to pronounced calcium auxotrophy. sltA sltB double null mutants display a cation stress sensitive phenotype indistinguishable from that of single slt mutants showing the close functional relationship between these two proteins. This functional relationship is reinforced by the fact that numerous mutations in both slt loci can be isolated as suppressors of poor colonial growth resulting from certain null vps (vacuolar protein sorting) mutations. In addition to allowing identification of sltB, our sltB missense mutations enabled prediction of functional regions in the SltB protein. Although the relationship between the Slt and Vps pathways remains enigmatic, absence of SltB, like that of SltA, leads to vacuolar hypertrophy. Importantly, the phenotypes of selected sltA and sltB mutations demonstrate that suppression of null vps mutations is not dependent on the inability to tolerate cation stress. Thus a specific role for both SltA and SltB in the VPS pathway seems likely. Finally, it is noteworthy that SltA and SltB have a similar, limited phylogenetic distribution, being restricted to

Tributyltin and triphenyltin inhibit osteoclast differentiation through a retinoic acid receptor-dependent signaling pathway

International Nuclear Information System (INIS)

Yonezawa, Takayuki; Hasegawa, Shin-ichi; Ahn, Jae-Yong; Cha, Byung-Yoon; Teruya, Toshiaki; Hagiwara, Hiromi; Nagai, Kazuo; Woo, Je-Tae

2007-01-01

Organotin compounds, such as tributyltin (TBT) and triphenyltin (TPT), have been widely used in agriculture and industry. Although these compounds are known to have many toxic effects, including endocrine-disrupting effects, their effects on bone resorption are unknown. In this study, we investigated the effects of organotin compounds, such as monobutyltin (MBT), dibutyltin (DBT), TBT, and TPT, on osteoclast differentiation using mouse monocytic RAW264.7 cells. MBT and DBT had no effects, whereas TBT and TPT dose-dependently inhibited osteoclast differentiation at concentrations of 3-30 nM. Treatment with a retinoic acid receptor (RAR)-specific antagonist, Ro41-5253, restored the inhibition of osteoclastogenesis by TBT and TPT. TBT and TPT reduced receptor activator of nuclear factor-κB ligand (RANKL) induced nuclear factor of activated T cells (NFAT) c1 expression, and the reduction in NFATc1 expression was recovered by Ro41-5253. Our results suggest that TBT and TPT suppress osteoclastogenesis by inhibiting RANKL-induced NFATc1 expression via an RAR-dependent signaling pathway

Bifunctional Alkylating Agent-Induced p53 and Nonclassical Nuclear Factor kB Responses and Cell Death are Altered by Caffeic Acid Phenethyl Ester: A Potential Role for Antioxidant/Electrophilic Response-Element Signaling

National Research Council Canada - National Science Library

Minsavage, Gary D; Dillman III, James F

2007-01-01

...) occurred within 5 min after exposure to tumor necrosis factor-alpha. However, exposure to BFA induced nonclassical NF-kB signaling as loss of IkBa was not observed until 2 or 6 h in NHEK or HaCaT cells, respectively...

Age dependent food consumption data provided for the computation of the radiological impact via the ingestion pathway

International Nuclear Information System (INIS)

Kalckbrenner, R.; Bayer, A.

1979-08-01

Averaged age dependent food consumption data are compiled and evaluated to provide input data for the computation of the radiological impact via the ingestion pathway. For special population groups (self-suppliers e.g.) factors are provided, by which the consumption for special foods may be exceeded. The evaluated data are compared with those of the 'USNRC-Regulatory Guide 1.109 (revised 1977)' and those of the 'Recommendation of the German Commission on Radiological Protection (Draft 1977)'. (orig.) [de

A Comparison of Hybrid Reynolds Averaged Navier Stokes/Large Eddy Simulation (RANS/LES) and Unsteady RANS Predictions of Separated Flow for a Variable Speed Power Turbine Blade Operating with Low Inlet Turbulence Levels

Science.gov (United States)

2017-10-01

6 4 3 passage 4 passage 5 passage 3 Sta. 0 Sta. 2 −2.0 0.0 −55.5°m etal −1.0 y  pitch β 1= 34. 2 ° z ero i β1=−11.8°max i β1=−2.5° t-o β 1 =4 0.0...structured grids at 2 flow conditions, cruise and takeoff, of the VSPT blade. Computations were run in parallel on a Department of Defense...to predict the separation/reattachment suggested by experiment. The difference in results between the 2 grids for RANS computations suggests that

Benchmarking pathway interaction network for colorectal cancer to identify dysregulated pathways

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Q. Wang

Full Text Available Different pathways act synergistically to participate in many biological processes. Thus, the purpose of our study was to extract dysregulated pathways to investigate the pathogenesis of colorectal cancer (CRC based on the functional dependency among pathways. Protein-protein interaction (PPI information and pathway data were retrieved from STRING and Reactome databases, respectively. After genes were aligned to the pathways, each pathway activity was calculated using the principal component analysis (PCA method, and the seed pathway was discovered. Subsequently, we constructed the pathway interaction network (PIN, where each node represented a biological pathway based on gene expression profile, PPI data, as well as pathways. Dysregulated pathways were then selected from the PIN according to classification performance and seed pathway. A PIN including 11,960 interactions was constructed to identify dysregulated pathways. Interestingly, the interaction of mRNA splicing and mRNA splicing-major pathway had the highest score of 719.8167. Maximum change of the activity score between CRC and normal samples appeared in the pathway of DNA replication, which was selected as the seed pathway. Starting with this seed pathway, a pathway set containing 30 dysregulated pathways was obtained with an area under the curve score of 0.8598. The pathway of mRNA splicing, mRNA splicing-major pathway, and RNA polymerase I had the maximum genes of 107. Moreover, we found that these 30 pathways had crosstalks with each other. The results suggest that these dysregulated pathways might be used as biomarkers to diagnose CRC.

Poliovirus trafficking toward central nervous system via human poliovirus receptor-dependent and -independent pathway.

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Seii eOHKA

2012-04-01

Full Text Available In humans, paralytic poliomyelitis results from the invasion of the central nervous system by circulating poliovirus (PV via the blood-brain barrier (BBB. After the virus enters the central nervous system (CNS, it replicates in neurons, especially in motor neurons (MNs, inducing the cell death that causes paralytic poliomyelitis. Along with this route of dissemination, neural pathway has been reported in humans, monkeys, and PV-sensitive human PV receptor (hPVR/CD155-transgenic (Tg mice. We demonstrated that a fast retrograde axonal transport process is required for PV dissemination through the sciatic nerve of hPVR-Tg mice and that intramuscularly inoculated PV causes paralysis in a hPVR-dependent manner. We also showed that hPVR-independent axonal transport of PV exists in hPVR-Tg and non-Tg mice, indicating that several different pathways for PV axonal transport exist in these mice. Circulating PV after intravenous inoculation in mice cross the BBB at a high rate in a hPVR-independent manner. Recently, we identified transferrin receptor 1 (TfR1 of mouse brain capillary endothelial cells as a binding protein to PV, implicating that TfR1 is a possible receptor for PV to permeate the BBB.

Reynolds Averaged Navier-Stokes (RANS) equation solutions of wind turbine wakes

Energy Technology Data Exchange (ETDEWEB)

Ludwig, Daniel Evandro; Horn, Diego Anderson; Petry, Adriane Prisco [Thermal and Energy Study Group, Mechanical Engeneering Department, Federal University of Rio Grande do Sul, Porto Alegre (Brazil)], E-mail: adrianep@mecanica.ufrgs.br

2010-07-01

This paper aims to evaluate the influence of three different turbulence models in the study of a wind turbine wake. Numerical Simulation is used as working tool to characterize the flow through the wind turbines, it is used the numeric simulation. The numerical analysis is based on the finite volume method and the Reynolds Averaged Navier-Stokes (RANS) equations. Three turbulence models are used to represent the total effects of turbulence in the flow: the two equations k-classical and the RNG k- models, based on the turbulent viscosity; and the Shear Stress Transport (SST) model, based on the transport of the Reynolds tensor. The results of the 'u' velocity profiles are compared to experimental data from Vermeer (2003) at distances equivalent to 2, 4, 6, 8, 10 and 16 diameters downstream from the turbine. Results shows that the SST model gives better results until 6 diameters, beyond this distance there is no significant differences between the compared models. (author)

Real-time cell toxicity profiling of Tox21 10K compounds reveals cytotoxicity dependent toxicity pathway linkage.

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Jui-Hua Hsieh

Full Text Available Cytotoxicity is a commonly used in vitro endpoint for evaluating chemical toxicity. In support of the U.S. Tox21 screening program, the cytotoxicity of ~10K chemicals was interrogated at 0, 8, 16, 24, 32, & 40 hours of exposure in a concentration dependent fashion in two cell lines (HEK293, HepG2 using two multiplexed, real-time assay technologies. One technology measures the metabolic activity of cells (i.e., cell viability, glo while the other evaluates cell membrane integrity (i.e., cell death, flor. Using glo technology, more actives and greater temporal variations were seen in HEK293 cells, while results for the flor technology were more similar across the two cell types. Chemicals were grouped into classes based on their cytotoxicity kinetics profiles and these classes were evaluated for their associations with activity in the Tox21 nuclear receptor and stress response pathway assays. Some pathways, such as the activation of H2AX, were associated with the fast-responding cytotoxicity classes, while others, such as activation of TP53, were associated with the slow-responding cytotoxicity classes. By clustering pathways based on their degree of association to the different cytotoxicity kinetics labels, we identified clusters of pathways where active chemicals presented similar kinetics of cytotoxicity. Such linkages could be due to shared underlying biological processes between pathways, for example, activation of H2AX and heat shock factor. Others involving nuclear receptor activity are likely due to shared chemical structures rather than pathway level interactions. Based on the linkage between androgen receptor antagonism and Nrf2 activity, we surmise that a subclass of androgen receptor antagonists cause cytotoxicity via oxidative stress that is associated with Nrf2 activation. In summary, the real-time cytotoxicity screen provides informative chemical cytotoxicity kinetics data related to their cytotoxicity mechanisms, and with our

Intraganglionic signaling as a novel nasal-meningeal pathway for TRPA1-dependent trigeminovascular activation by inhaled environmental irritants.

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Phillip Edward Kunkler

Full Text Available Headache is the most common symptom associated with air pollution, but little is understood about the underlying mechanism. Nasal administration of environmental irritants activates the trigeminovascular system by a TRPA1-dependent process. This report addresses questions about the anatomical pathway involved and the function of TRP channels in this pathway. TRPV1 and TRPA1 are frequently co-localized and interact to modulate function in sensory neurons. We demonstrate here that resiniferatoxin ablation of TRPV1 expressing neurons significantly reduces meningeal blood flow responses to nasal administration of both TRPV1 and TRPA1 agonists. Accordingly resiniferatoxin also significantly reduces TRPV1 and CGRP immunostaining and TRPV1 and TRPA1 message levels in trigeminal ganglia. Sensory neurons of the trigeminal ganglia innervate the nasal epithelium and the meninges, but the mechanism and anatomical route by which nasal administration evokes meningeal vasodilatation is unclear. Double retrograde labeling from the nose and meninges reveals no co-localization of fluorescent label, however nasal and meningeal labeled cells are located in close proximity to each other within the trigeminal ganglion. Our data demonstrate that TRPV1 expressing neurons are important for TRPA1 responses in the nasal-meningeal pathway. Our data also suggest that the nasal-meningeal pathway is not primarily by axon reflex, but may instead result from intraganglionic transmission.

Viral delivery of C9orf72 hexanucleotide repeat expansions in mice leads to repeat-length-dependent neuropathology and behavioural deficits

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Saul Herranz-Martin

2017-07-01

Full Text Available Intronic GGGGCC repeat expansions in C9orf72 are the most common genetic cause of amyotrophic lateral sclerosis (ALS and frontotemporal dementia (FTD. Two major pathologies stemming from the hexanucleotide RNA expansions (HREs have been identified in postmortem tissue: intracellular RNA foci and repeat-associated non-ATG dependent (RAN dipeptides, although it is unclear how these and other hallmarks of disease contribute to the pathophysiology of neuronal injury. Here, we describe two novel lines of mice that overexpress either 10 pure or 102 interrupted GGGGCC repeats mediated by adeno-associated virus (AAV and recapitulate the relevant human pathology and disease-related behavioural phenotypes. Similar levels of intracellular RNA foci developed in both lines of mice, but only mice expressing 102 repeats generated C9orf72 RAN pathology, neuromuscular junction (NMJ abnormalities, dispersal of the hippocampal CA1, enhanced apoptosis, and deficits in gait and cognition. Neither line of mice, however, showed extensive TAR DNA-binding protein 43 (TDP-43 pathology or neurodegeneration. Our data suggest that RNA foci pathology is not a good predictor of C9orf72 RAN dipeptide formation, and that RAN dipeptides and NMJ dysfunction are drivers of C9orf72 disease pathogenesis. These AAV-mediated models of C9orf72-associated ALS/FTD will be useful tools for studying disease pathophysiology and developing new therapeutic approaches.

Cardiotonic steroids trigger non-classical testosterone signaling in Sertoli cells via the α4 isoform of the sodium pump.

Science.gov (United States)

Konrad, Lutz; Dietze, Raimund; Kirch, Ulrike; Kirch, Herbert; Eva, Alexander; Scheiner-Bobis, Georgios

2011-12-01

The α4 isoform of the Na(+),K(+)-ATPase (sodium pump) is known to be expressed in spermatozoa and to be critical for their motility. In the investigation presented here, we find that the rat-derived Sertoli cell line 93RS2 also expresses considerable amounts of the α4 isoform in addition to the α1 isoform. Since Sertoli cells are not motile, one can assume that the function of the α4 isoform in these cells must differ from that in spermatozoa. Thus, we assessed a potential involvement of this isoform in signaling pathways that are activated by the cardiotonic steroid (CTS) ouabain, a highly specific sodium pump ligand. Treatment of 93RS2 cells with ouabain leads to activation of the c-Src/c-Raf/Erk1/2 signaling cascade. Furthermore, we show for the first time that the activation of this cascade by ouabain results in phosphorylation and activation of the transcription factor CREB. This signaling cascade is induced at low nanomolar concentrations of ouabain, consistent with the involvement of the α4 isoform. This is further supported by experiments involving siRNA: silencing of α4 expression entirely blocks ouabain-induced activation of Erk1/2 whereas silencing of α1 has no effect. The findings of this study unveil new aspects in CTS/sodium pump interactions by demonstrating for the first time ouabain-induced signaling through the α4 isoform. The c-Src/c-Raf/Erk1/2/CREB cascade activated by ouabain is identical to the so-called non-classical signaling cascade that is normally triggered in Sertoli cells by testosterone. Taking into consideration that CTS are produced endogenously, our results may help to gain new insights into the physiological mechanisms associated with male fertility and reproduction. Copyright © 2011 Elsevier B.V. All rights reserved.

Towards the unified non-classical physics: account for quantum fluctuations in equilibrium thermodynamics via the effective temperature

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Yu.G.Rudoy

2005-01-01

Full Text Available The concept of effective temperature (ET T*(T0, T is used in order to approximately "quantize" the thermodynamic functions of the dynamical object which is in the thermal equilibrium with thermal bath being at constant temperature T (T0=E0/kB, where E0 is the ground-state energy, kB - Boltzmann constant, is the characteristic ``quantum'' temperature of the system itself. On these grounds the extensive comparative investigation is carried out for the ``standard model'' of statistical mechanics - the one-dimensional harmonic oscillator (HO. Three well-known approaches are considered and their thermodynamic consequences thoroughly studied. These are: the exact quantum, or non-classical Planck-Einstein approach, intermediate, or semiclassical Bloch-Wigner approach and, finally, the pure classical, or Maxwell-Boltzmann approach.

Is the anomalous magnetic moment the consequence of a non-classical transformation for rotating frames?

International Nuclear Information System (INIS)

Gisin, B V

2002-01-01

We consider the anomalous magnetic moment from an 'optical viewpoint' using an analogy between the motion of a particle with a magnetic moment in a magnetic field and the propagation of an optical pulse through an electro-optical crystal in an electric field. We show that an optical experiment similar to electron magnetic resonance is possible in some electro-optical crystals possessing the Faraday effect. This phenomenon is described by an analogue of the Pauli equation extracted from the Maxwell equation in the slowly varied amplitude approximation. In such an experiment the modulation by rotating fields plays a significant role. From the optical viewpoint the modulation assumes introducing the concept of a point rotation frame with the rotation axis at every point originated from the concept of the optical indicatrix (index ellipsoid). We discuss the connection between the non-classical transformation by transition from one such frame to another and an anomalous magnetic moment

FGF1 protects neuroblastoma SH-SY5Y cells from p53-dependent apoptosis through an intracrine pathway regulated by FGF1 phosphorylation

Science.gov (United States)

Pirou, Caroline; Montazer-Torbati, Fatemeh; Jah, Nadège; Delmas, Elisabeth; Lasbleiz, Christelle; Mignotte, Bernard; Renaud, Flore

2017-01-01

Neuroblastoma, a sympathetic nervous system tumor, accounts for 15% of cancer deaths in children. In contrast to most human tumors, p53 is rarely mutated in human primary neuroblastoma, suggesting impaired p53 activation in neuroblastoma. Various studies have shown correlations between fgf1 expression levels and both prognosis severity and tumor chemoresistance. As we previously showed that fibroblast growth factor 1 (FGF1) inhibited p53-dependent apoptosis in neuron-like PC12 cells, we initiated the study of the interaction between the FGF1 and p53 pathways in neuroblastoma. We focused on the activity of either extracellular FGF1 by adding recombinant rFGF1 in media, or of intracellular FGF1 by overexpression in human SH-SY5Y and mouse N2a neuroblastoma cell lines. In both cell lines, the genotoxic drug etoposide induced a classical mitochondrial p53-dependent apoptosis. FGF1 was able to inhibit p53-dependent apoptosis upstream of mitochondrial events in SH-SY5Y cells by both extracellular and intracellular pathways. Both rFGF1 addition and etoposide treatment increased fgf1 expression in SH-SY5Y cells. Conversely, rFGF1 or overexpressed FGF1 had no effect on p53-dependent apoptosis and fgf1 expression in neuroblastoma N2a cells. Using different FGF1 mutants (that is, FGF1K132E, FGF1S130A and FGF1S130D), we further showed that the C-terminal domain and phosphorylation of FGF1 regulate its intracrine anti-apoptotic activity in neuroblastoma SH-SY5Y cells. This study provides the first evidence for a role of an intracrine growth factor pathway on p53-dependent apoptosis in neuroblastoma, and could lead to the identification of key regulators involved in neuroblastoma tumor progression and chemoresistance. PMID:29048426

Response of tobacco to the Pseudomonas syringae pv. Tomato DC3000 is mainly dependent on salicylic acid signaling pathway.

Science.gov (United States)

Liu, Yang; Wang, Li; Cai, Guohua; Jiang, Shanshan; Sun, Liping; Li, Dequan

2013-07-01

Pseudomonas syringae pv. Tomato DC3000 (Pst DC3000) was the first pathogen to be demonstrated to infect Arabidopsis and to cause disease symptoms in the laboratory setting. However, the defense response to Pst DC3000 was unclear in tobacco. In this report, the expression profiles of twelve defense response-related genes were analyzed after treatment with salicylic acid (SA), jasmonic acid (JA), and pathogen Pst DC3000 by qRT-PCR. According to our results, it could be presented that the genes primarily induced by SA were also induced to higher levels after Pst DC3000 infection. SA accumulation could be induced to a higher level than that of JA after Pst DC3000 infection. In addition, SA could result in hypersensitive response (HR), which did not completely depend on accumulation of reactive oxygen species. These results indicated that tobacco mainly depended on SA signaling pathway rather than on JA signaling pathway in response to Pst DC3000. Further study demonstrated that JA could significantly inhibit the accumulation of SA and the generation of the HR induced by Pst DC3000. © 2013 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

T3SS-dependent differential modulations of the jasmonic acid pathway in susceptible and resistant genotypes of Malus spp. challenged with Erwinia amylovora.

Science.gov (United States)

Dugé De Bernonville, Thomas; Gaucher, Matthieu; Flors, Victor; Gaillard, Sylvain; Paulin, Jean-Pierre; Dat, James F; Brisset, Marie-Noëlle

2012-06-01

Fire blight is a bacterial disease of Maloideae caused by Erwinia amylovora (Ea). This necrogenic enterobacterium uses a type III secretion system (T3SS) to inject type III effectors into the plant cells to cause disease on its susceptible hosts, including economically important crops like apple and pear. The expressions of marker genes of the salicylic acid (SA) and jasmonic acid (JA) defense regulation pathways were monitored by RT-qPCR in leaves of two apple genotypes, one susceptible and one resistant, challenged with a wild type strain, a T3SS-deficient strain or water. The transcriptional data taken together with hormone level measurements indicated that the SA pathway was similarly induced in both apple genotypes during infection by Ea. On the contrary, the data clearly showed a strong T3SS-dependent down-regulation of the JA pathway in leaves of the susceptible genotype but not in those of the resistant one. Accordingly, methyl-jasmonate treated susceptible plants displayed an increased resistance to Ea. Bacterial mutant analysis indicated that JA manipulation by Ea mainly relies on the type III effector DspA/E. Taken together, our data suggest that the T3SS-dependent down-regulation of the JA pathway is a critical step in the infection process of Malus spp. by Ea. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

ATP-dependent human RISC assembly pathways.

Science.gov (United States)

Yoda, Mayuko; Kawamata, Tomoko; Paroo, Zain; Ye, Xuecheng; Iwasaki, Shintaro; Liu, Qinghua; Tomari, Yukihide

2010-01-01

The assembly of RNA-induced silencing complex (RISC) is a key process in small RNA-mediated gene silencing. In humans, small interfering RNAs (siRNAs) and microRNAs (miRNAs) are incorporated into RISCs containing the Argonaute (AGO) subfamily proteins Ago1-4. Previous studies have proposed that, unlike Drosophila melanogaster RISC assembly pathways, human RISC assembly is coupled with dicing and is independent of ATP. Here we show by careful reexamination that, in humans, RISC assembly and dicing are uncoupled, and ATP greatly facilitates RISC loading of small-RNA duplexes. Moreover, all four human AGO proteins show remarkably similar structural preferences for small-RNA duplexes: central mismatches promote RISC loading, and seed or 3'-mid (guide position 12-15) mismatches facilitate unwinding. All these features of human AGO proteins are highly reminiscent of fly Ago1 but not fly Ago2.

BID links ferroptosis to mitochondrial cell death pathways

NARCIS (Netherlands)

Neitemeier, Sandra; Jelinek, Anja; Laino, Vincenzo; Hoffmann, Lena; Eisenbach, Ina; Eying, Roman; Ganjam, Goutham K; Dolga, Amalia M; Oppermann, Sina; Culmsee, Carsten

2017-01-01

Ferroptosis has been defined as an oxidative and iron-dependent pathway of regulated cell death that is distinct from caspase-dependent apoptosis and established pathways of death receptor-mediated regulated necrosis. While emerging evidence linked features of ferroptosis induced e.g. by

Simian hemorrhagic fever virus cell entry is dependent on CD163 and uses a clathrin-mediated endocytosis-like pathway.

Science.gov (United States)

Caì, Yíngyún; Postnikova, Elena N; Bernbaum, John G; Yú, Shu Qìng; Mazur, Steven; Deiuliis, Nicole M; Radoshitzky, Sheli R; Lackemeyer, Matthew G; McCluskey, Adam; Robinson, Phillip J; Haucke, Volker; Wahl-Jensen, Victoria; Bailey, Adam L; Lauck, Michael; Friedrich, Thomas C; O'Connor, David H; Goldberg, Tony L; Jahrling, Peter B; Kuhn, Jens H

2015-01-01

Simian hemorrhagic fever virus (SHFV) causes a severe and almost uniformly fatal viral hemorrhagic fever in Asian macaques but is thought to be nonpathogenic for humans. To date, the SHFV life cycle is almost completely uncharacterized on the molecular level. Here, we describe the first steps of the SHFV life cycle. Our experiments indicate that SHFV enters target cells by low-pH-dependent endocytosis. Dynamin inhibitors, chlorpromazine, methyl-β-cyclodextrin, chloroquine, and concanamycin A dramatically reduced SHFV entry efficiency, whereas the macropinocytosis inhibitors EIPA, blebbistatin, and wortmannin and the caveolin-mediated endocytosis inhibitors nystatin and filipin III had no effect. Furthermore, overexpression and knockout study and electron microscopy results indicate that SHFV entry occurs by a dynamin-dependent clathrin-mediated endocytosis-like pathway. Experiments utilizing latrunculin B, cytochalasin B, and cytochalasin D indicate that SHFV does not hijack the actin polymerization pathway. Treatment of target cells with proteases (proteinase K, papain, α-chymotrypsin, and trypsin) abrogated entry, indicating that the SHFV cell surface receptor is a protein. Phospholipases A2 and D had no effect on SHFV entry. Finally, treatment of cells with antibodies targeting CD163, a cell surface molecule identified as an entry factor for the SHFV-related porcine reproductive and respiratory syndrome virus, diminished SHFV replication, identifying CD163 as an important SHFV entry component. Simian hemorrhagic fever virus (SHFV) causes highly lethal disease in Asian macaques resembling human illness caused by Ebola or Lassa virus. However, little is known about SHFV's ecology and molecular biology and the mechanism by which it causes disease. The results of this study shed light on how SHFV enters its target cells. Using electron microscopy and inhibitors for various cellular pathways, we demonstrate that SHFV invades cells by low-pH-dependent, actin

Identification of altered pathways in breast cancer based on individualized pathway aberrance score.

Science.gov (United States)

Shi, Sheng-Hong; Zhang, Wei; Jiang, Jing; Sun, Long

2017-08-01

The objective of the present study was to identify altered pathways in breast cancer based on the individualized pathway aberrance score (iPAS) method combined with the normal reference (nRef). There were 4 steps to identify altered pathways using the iPAS method: Data preprocessing conducted by the robust multi-array average (RMA) algorithm; gene-level statistics based on average Z ; pathway-level statistics according to iPAS; and a significance test dependent on 1 sample Wilcoxon test. The altered pathways were validated by calculating the changed percentage of each pathway in tumor samples and comparing them with pathways from differentially expressed genes (DEGs). A total of 688 altered pathways with Ppathways were involved in the total 688 altered pathways, which may validate the present results. In addition, there were 324 DEGs and 155 common genes between DEGs and pathway genes. DEGs and common genes were enriched in the same 9 significant terms, which also were members of altered pathways. The iPAS method was suitable for identifying altered pathways in breast cancer. Altered pathways (such as KIF and PLK mediated events) were important for understanding breast cancer mechanisms and for the future application of customized therapeutic decisions.

Contribution of the D-Serine-dependent pathway to the cellular mechanisms underlying cognitive aging

Directory of Open Access Journals (Sweden)

Emilie Rouaud

2010-02-01

Full Text Available An association between age-related memory impairments and changes in functional plasticity in the aging brain has been under intense study within the last decade. In this article, we show that an impaired activation of the strychnine-insensitive glycine site of N-Methyl-D-Aspartate receptors (NMDA-R by its agonist D-serine contributes to deficits of synaptic plasticity in the hippocampus of memory-impaired aged rats. Supplementation with exogenous D-serine prevents the age-related deficits of isolated NMDA-R-dependent synaptic potentials as well as those of theta-burst-induced long-term potentiation and synaptic depotentiation. Endogenous levels of D-serine are reduced in the hippocampus with aging, that correlates with a weaker expression of serine racemase synthesizing the amino acid. On the contrary, the affinity of D-serine binding to NMDA-R is not affected by aging. These results point to a critical role for the D-serine-dependent pathway in the functional alterations of the brain underlying memory impairment and provide key information in the search for new therapeutic strategies for the treatment of memory deficits in the elderly.

Pathway Interaction Network Analysis Identifies Dysregulated Pathways in Human Monocytes Infected by Listeria monocytogenes

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Wufeng Fan

2017-01-01

Full Text Available In our study, we aimed to extract dysregulated pathways in human monocytes infected by Listeria monocytogenes (LM based on pathway interaction network (PIN which presented the functional dependency between pathways. After genes were aligned to the pathways, principal component analysis (PCA was used to calculate the pathway activity for each pathway, followed by detecting seed pathway. A PIN was constructed based on gene expression profile, protein-protein interactions (PPIs, and cellular pathways. Identifying dysregulated pathways from the PIN was performed relying on seed pathway and classification accuracy. To evaluate whether the PIN method was feasible or not, we compared the introduced method with standard network centrality measures. The pathway of RNA polymerase II pretranscription events was selected as the seed pathway. Taking this seed pathway as start, one pathway set (9 dysregulated pathways with AUC score of 1.00 was identified. Among the 5 hub pathways obtained using standard network centrality measures, 4 pathways were the common ones between the two methods. RNA polymerase II transcription and DNA replication owned a higher number of pathway genes and DEGs. These dysregulated pathways work together to influence the progression of LM infection, and they will be available as biomarkers to diagnose LM infection.

Signaling flux redistribution at toll-like receptor pathway junctions.

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Kumar Selvarajoo

Full Text Available Various receptors on cell surface recognize specific extracellular molecules and trigger signal transduction altering gene expression in the nucleus. Gain or loss-of-function mutations of one molecule have shown to affect alternative signaling pathways with a poorly understood mechanism. In Toll-like receptor (TLR 4 signaling, which branches into MyD88- and TRAM-dependent pathways upon lipopolysaccharide (LPS stimulation, we investigated the gain or loss-of-function mutations of MyD88. We predict, using a computational model built on the perturbation-response approach and the law of mass conservation, that removal and addition of MyD88 in TLR4 activation, enhances and impairs, respectively, the alternative TRAM-dependent pathway through signaling flux redistribution (SFR at pathway branches. To verify SFR, we treated MyD88-deficient macrophages with LPS and observed enhancement of TRAM-dependent pathway based on increased IRF3 phosphorylation and induction of Cxcl10 and Ifit2. Furthermore, increasing the amount of MyD88 in cultured cells showed decreased TRAM binding to TLR4. Investigating another TLR4 pathway junction, from TRIF to TRAF6, RIP1 and TBK1, the removal of MyD88-dependent TRAF6 increased expression of TRAM-dependent Cxcl10 and Ifit2. Thus, we demonstrate that SFR is a novel mechanism for enhanced activation of alternative pathways when molecules at pathway junctions are removed. Our data suggest that SFR may enlighten hitherto unexplainable intracellular signaling alterations in genetic diseases where gain or loss-of-function mutations are observed.

Molecular network, pathway, and functional analysis of time-dependent gene changes associated with pancreatic cancer susceptibility to oncolytic vaccinia virotherapy

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Dana Haddad

2016-01-01

Conclusions: Our study reveals the ability to assess time-dependent changes in gene expression patterns in pancreatic cancer cells associated with infection and susceptibility to vaccinia viruses. This suggests that molecular assays may be useful to develop safer and more efficacious oncolyticvirotherapies and support the idea that these treatments may target pathways implicated in pancreatic cancer resistance to conventional therapies.

Fluxes of Ca2+ and K+ are required for the listeriolysin O-dependent internalization pathway of Listeria monocytogenes.

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Vadia, Stephen; Seveau, Stephanie

2014-03-01

Listeria monocytogenes is responsible for the life-threatening food-borne disease listeriosis. This disease mainly affects elderly and immunocompromised individuals, causing bacteremia and meningoencephalitis. In pregnant women, L. monocytogenes infection leads to abortion and severe infection of the fetus or newborn. The L. monocytogenes intracellular life cycle is critical for pathogenesis. Previous studies have established that the major virulence factor of L. monocytogenes, the pore-forming toxin listeriolysin O (LLO), is sufficient to induce L. monocytogenes internalization into human epithelial cell lines. This internalization pathway strictly requires the formation of LLO pores in the plasma membrane and can be stimulated by the heterologous pore-forming toxin pneumolysin, suggesting that LLO acts nonspecifically by forming transmembrane pores. The present work tested the hypothesis that Ca2+ and K+ fluxes subsequent to perforation by LLO control L. monocytogenes internalization. We report that L. monocytogenes perforates the host cell plasma membrane in an LLO-dependent fashion at the early stage of invasion. In response to perforation, host cells undergo Ca2+ -dependent but K+ -independent resealing of their plasma membrane. In contrast to the plasma membrane resealing process, LLO-induced L. monocytogenes internalization requires both Ca2+ and K+ fluxes. Further linking ion fluxes to bacterial internalization, treating cells with a combination of Ca2+ and K+ ionophores but not with individual ionophores is sufficient to induce efficient internalization of large cargoes, such as 1-μm polystyrene beads and bacteria. We propose that LLO-induced L. monocytogenes internalization requires a Ca2+ - and K+ -dependent internalization pathway that is mechanistically distinct from the process of plasma membrane resealing.

Mefloquine effectively targets gastric cancer cells through phosphatase-dependent inhibition of PI3K/Akt/mTOR signaling pathway

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Liu, Yanwei [Department of General Surgery, Shiyan Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei Province (China); Chen, Sen [Department of Academic Affairs, Hubei University of Medicine, Shiyan, Hubei Province (China); Xue, Rui [Department of Anesthesiology, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei Province (China); Zhao, Juan [Department of Oncology, Xiangyang Central Hospital, Shiyan, Hubei Province (China); Di, Maojun, E-mail: maoojun_di@163.com [Department of General Surgery, Shiyan Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei Province (China)

2016-02-05

Deregulation of PI3K/Akt/mTOR pathway has been recently identified to play a crucial role in the progress of human gastric cancer. In this study, we show that mefloquine, a FDA-approved anti-malarial drug, effectively targets human gastric cancer cells. Mefloquine potently inhibits proliferation and induces apoptosis of a panel of human gastric cancer cell lines, with EC{sub 50} ∼0.5–0.7 μM. In two independent gastric cancer xenograft mouse models, mefloquine significantly inhibits growth of both tumors. The combination of mefloquine with paclitaxel enhances the activity of either drug alone in in vitro and in vivo. In addition, mefloquine potently decreased phosphorylation of PI3K, Akt, mTOR and rS6. Overexpression of constitutively active Akt significantly restored mefloquine-mediated inhibition of mTOR phosphorylation and growth, and induction of apoptosis, suggesting that mefloquine acts on gastric cancer cells via suppressing PI3K/Akt/mTOR pathway. We further show that mefloquine-mediated inhibition of Akt/mTOR singaling is phosphatase-dependent as pretreatment with calyculin A does-dependently reversed mefloquine-mediated inhibition of Akt/mTOR phosphorylation. Since mefloquine is already available for clinic use, these results suggest that it is a useful addition to the treatment armamentarium for gastric cancer. - Highlights: • Mefloquine targets a panel of gastric cancer cell lines in vitro and in vivo. • Combination of mefloquine and paclitaxel is synergistic. • Mefloquine acts on gastric cancer via inhibition of PI3K/Akt/mTOR pathway. • Mefloquine can be repurposed for gastric cancer treatment.

LES and RANS modeling of pulverized coal combustion in swirl burner for air and oxy-combustion technologies

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Warzecha, Piotr; Boguslawski, Andrzej

2014-01-01

Combustion of pulverized coal in oxy-combustion technology is one of the effective ways to reduce the emission of greenhouse gases into the atmosphere. The process of transition from conventional combustion in air to the oxy-combustion technology, however, requires a thorough investigations of the phenomena occurring during the combustion process, that can be greatly supported by numerical modeling. The paper presents the results of numerical simulations of pulverized coal combustion process in swirl burner using RANS (Reynolds-averaged Navier–Stokes equations) and LES (large Eddy simulation) methods for turbulent flow. Numerical simulations have been performed for the oxyfuel test facility located at the Institute of Heat and Mass Transfer at RWTH Aachen University. Detailed analysis of the flow field inside the combustion chamber for cold flow and for the flow with combustion using different numerical methods for turbulent flows have been done. Comparison of the air and oxy-coal combustion process for pulverized coal shows significant differences in temperature, especially close to the burner exit. Additionally the influence of the combustion model on the results has been shown for oxy-combustion test case. - Highlights: • Oxy-coal combustion has been modeled for test facility operating at low oxygen ratio. • Coal combustion process has been modeled with simplified combustion models. • Comparison of oxy and air combustion process of pulverized coal has been done. • RANS (Reynolds-averaged Navier–Stokes equations) and LES (large Eddy simulation) results for pulverized coal combustion process have been compared

CFD modelling approaches against single wind turbine wake measurements using RANS

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Stergiannis, N; Lacor, C; Beeck, J V; Donnelly, R

2016-01-01

Numerical simulations of two wind turbine generators including the exact geometry of their blades and hub are compared against a simplified actuator disk model (ADM). The wake expansion of the upstream rotor is investigated and compared with measurements. Computational Fluid Dynamics (CFD) simulations have been performed using the open-source platform OpenFOAM [1]. The multiple reference frame (MRF) approach was used to model the inner rotating reference frames in a stationary computational mesh and outer reference frame for the full wind turbine rotor simulations. The standard k — ε and k — ω turbulence closure schemes have been used to solve the steady state, three dimensional Reynolds Averaged Navier- Stokes (RANS) equations. Results of near and far wake regions are compared with wind tunnel measurements along three horizontal lines downstream. The ADM under-predicted the velocity deficit at the wake for both turbulence models. Full wind turbine rotor simulations showed good agreement against the experimental data at the near wake, amplifying the differences between the simplified models. (paper)

Nano rare-earth oxides induced size-dependent vacuolization: an independent pathway from autophagy.

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Zhang, Ying; Yu, Chenguang; Huang, Guanyi; Wang, Changli; Wen, Longping

2010-09-07

Four rare earth oxides have been shown to induce autophagy. Interestingly, we often noticed plentiful vacuolization, which was not always involved in this autophagic process. In this study, we investigated three other rare-earth elements, including Yttrium (Y), Ytterbium (Yb), and Lanthanum (La). Autophagic effect could be induced by all of them but only Y(2)O(3) and Yb(2)O(3) could cause massive vacuolization. Y(2)O(3) and Yb(2)O(3) treated by sonication or centrifugation to reduce particle size were used to test vacuolization level in HeLa cell lines. The results showed that rare earth oxides-induced vacuolization is size-dependent and differs from autophagic pathway. To further clarify the characteristics of this autophagic process, we used MEF Atg-5 (autophagy associated gene 5) knockout cell line, and the result showed that the autophagic process induced by rare earth oxides is Atg-5-dependent and the observed vacuolization was independent from autophagy. Similar results could also be observed in our tests on 3-methyladenine(3-MA), a well-known autophagy inhibitor. In conclusion, for the first time, we clarified the relationship between massive vacuolization and autophagic process induced by rare earth oxides and pointed out the size effect of rare earth oxides on the formation of vacuoles, which give clues to further investigation on the mechanisms underlying their biological effects.

An ontology-driven semantic mashup of gene and biological pathway information: application to the domain of nicotine dependence.

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Sahoo, Satya S; Bodenreider, Olivier; Rutter, Joni L; Skinner, Karen J; Sheth, Amit P

2008-10-01

This paper illustrates how Semantic Web technologies (especially RDF, OWL, and SPARQL) can support information integration and make it easy to create semantic mashups (semantically integrated resources). In the context of understanding the genetic basis of nicotine dependence, we integrate gene and pathway information and show how three complex biological queries can be answered by the integrated knowledge base. We use an ontology-driven approach to integrate two gene resources (Entrez Gene and HomoloGene) and three pathway resources (KEGG, Reactome and BioCyc), for five organisms, including humans. We created the Entrez Knowledge Model (EKoM), an information model in OWL for the gene resources, and integrated it with the extant BioPAX ontology designed for pathway resources. The integrated schema is populated with data from the pathway resources, publicly available in BioPAX-compatible format, and gene resources for which a population procedure was created. The SPARQL query language is used to formulate queries over the integrated knowledge base to answer the three biological queries. Simple SPARQL queries could easily identify hub genes, i.e., those genes whose gene products participate in many pathways or interact with many other gene products. The identification of the genes expressed in the brain turned out to be more difficult, due to the lack of a common identification scheme for proteins. Semantic Web technologies provide a valid framework for information integration in the life sciences. Ontology-driven integration represents a flexible, sustainable and extensible solution to the integration of large volumes of information. Additional resources, which enable the creation of mappings between information sources, are required to compensate for heterogeneity across namespaces. RESOURCE PAGE: http://knoesis.wright.edu/research/lifesci/integration/structured_data/JBI-2008/